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PubMed1981

The release of endogenous catecholamines in the cat hypothalamus is affected by spinal transection and drugs which change the arterial blood pressure.

1. In anesthetized cats, posterior and anterior hypothalamic areas were superfused with CSF through double-walled cannulae. The release of endogenous catecholamines (dopamine, noradrenaline and adrenaline) was determined in the superfusate by a radioenzymatic assay. 2. Transection of the brain caudal to the hypothalamus almost abolished the release of catecholamines in the posterior hypothalamic area, while that in the anterior hypothalamic area was moderately decreased. A circular transection around the hypothalamus greatly reduced the release of catecholamines in the anterior hypothalamic area. It is concluded that the catecholaminergic nerve endings of the anterior hypothalamic area do not originate entirely from cell bodies located in the brain stem. 3. Spinal transection elicited a pressor response which was followed by a fall of the arterial blood pressure. The pressor response was associated with increased rates of release of the catecholamines in the anterior hypothalamic area, while the release of catecholamines in the posterior hypothalamic area was reduced. The fall of blood pressure enhanced the rates of release of the catecholamines in the posterior hypothalamic area and reduced their release in the anterior hypothalamic area. 4. Chlorisondamine i.v. caused a fall of blood pressure which was associated with an increased release of catecholamines in the posterior hypothalamic area and a decrease in the rates of release in the anterior hypothalamic area whilst i.v. tramazoline elicited a pressor response and enhanced the rates of release of the catecholamines in the anterior hypothalamic area. 5. It is concluded that pronounced changes in the arterial blood pressure affect the release of catecholamine in opposite direction in the two hypothalamic areas to counteract the blood pressure change.

Animals↗
PubMed1973

Pentobarbitone inhibition of catecholamine secretion.

1. The perfused isolated cow adrenal gland was used to investigate the effect of barbituric acid, phenobarbitone and pentobarbitone on catecholamine secretion.2. Pentobarbitone reduced catecholamine secretion induced by a number of drugs which cause exocytosis. The concentration of pentobarbitone which caused a 50% inhibition of catecholamine secretion was for acetylcholine 5.6 x 10(-5)M, for carbachol 6.3 x 10(-5)M, for histamine 1.6 x 10(-4)M, for (+)-amphetamine 4.4 x 10(-5)M and for potassium chloride 1.5 x 10(-4)M. The degree of inhibition by pentobarbitone was not dependent on the concentration of the secretagogue.3. Pentobarbitone (up to 10(-3)M) did not inhibit the catecholamine release that was induced by acetyldehyde or by calcium chloride; it inhibited slightly (34%) the catecholamine secretion induced by tyramine.4. Catecholamine release induced by carbachol was also inhibited by phenobarbitone (50% inhibition at 2.8 x 10(-4)M (n=7)) but was unaffected by barbituric acid.5. Pentobarbitone had no effect on spontaneous or on (+)-amphetamine- or tyramine-induced release of catecholamines from isolated chromaffin vesicles of cow adrenal medulla.6. It is concluded that pentobarbitone inhibits catecholamine release by preventing a configurational change in the structure of the membrane of the chromaffin cell which is a necessary link between receptor activation and catecholamine release.

Acetylcholine↗
PubMed1976

The effect of catecholamines on the influx of calcium and the development of tension in denervated mouse diaphragm muscle.

1 The nature of the catecholamine-induced contracture of chronically denervated mouse diaphragm muscle has been investigated and compared with the contractural response evoked by acetylcholine. 2 The time course of onset of catecholamine-sensitivity in denervated diaphragm muscles was similar to the development of acetylcholine sensitivity. However, catecholamine contractures were absent in tissues denervated for periods longer than 90 days whereas acetylcholine-sensitivity was still evident several months after denervation. 3 The catecholamine-induced contracture of the denervated muscle was inhibited specifically by beta-receptor blocking drugs and was unaffected by alpha-receptor blocking drugs and cholinoceptor antagonists. 4 Catecholamine-induced contractures of denervated muscles, unlike contractures to acetylcholine, were dependent upon the presence of spontaneous fibrillation and the amplitude of spontaneous fibrillation was increased by catecholamines. Fibrillation was absent in the presence of tetrodotoxin (1 muM), 2,4-dinitrophenol (10 muM), potassium cyanide (10 muM), ouabain (100 muM), in lithium chloride Ringer solution and at low temperature. Under these conditions catecholamine-induced contractures, but not those to acetylcholine, were abolished. 5 Labelled calcium was found progressively to enter denervated muscle fibres and this entry of calcium was increased by catecholamines. It is suggested that this calcium entry may represent either an increased calcium permeability of denervated muscle fibres which is increased further by catecholamines or the presence of a calcium current that occurs during the fibrillatory potentials of denervated muscle.

Acetylcholine↗
PubMed1992

Comparisons of the effects of ryanodine on catecholamine secretion evoked by caffeine and acetylcholine in perfused adrenal glands of the guinea-pig.

1. The effect of ryanodine on catecholamine secretion induced by caffeine and muscarinic receptor activation was investigated in perfused adrenal glands of the guinea-pig. 2. Caffeine (40 mM) caused only a small increase in catecholamine secretion during perfusion with standard Locke solution. Caffeine-induced catecholamine secretion was markedly enhanced after removal of CaCl2 together with replacement of NaCl with sucrose. 3. In the absence of CaCl2 and NaCl, 50 microM ryanodine had no effect on the resting catecholamine secretion. Caffeine (40 mM) administered 15 min after treatment with ryanodine caused an increase in catecholamine secretion similar to that prior to application of ryanodine, but failed to have any effect thereafter. Combined application of ryanodine and caffeine also prevented catecholamine secretion induced by caffeine applied subsequently. 4. Catecholamine secretion induced by 100 microM acetylcholine (ACh) was only partially inhibited after treatment with ryanodine plus caffeine under Ca(2+)-free, Na(+)-deficient conditions. 5. Preferential influence of ryanodine on the response to caffeine was also confirmed in catecholamine secretion evoked by paired stimuli with caffeine and ACh alternately, during perfusion with either Ca(2+)-free Locke or sucrose-substituted solutions. 6. These results indicate that caffeine increases catecholamine secretion by mobilizing Ca2+ from intracellular Ca2+ stores through ryanodine-sensitive mechanisms in guinea-pig adrenal chromaffin cells. Ca2+ stores sensitive to caffeine and muscarinic receptor activation may not overlap entirely.

Acetylcholine↗
PubMed1992

Relationship between blood O2 content and catecholamine levels during hypoxia in rainbow trout and American eel.

Plasma catecholamine levels and arterial blood respiratory variables were monitored in rainbow trout (Oncorhynchus mykiss) and American eel (Anguilla rostrata) acutely exposed (30 min) to graded levels of external hypoxia [water PO2 (PWO2) 20-90 Torr]. The experiments were designed to evaluate the factors controlling catecholamine mobilization in hypoxic fish and to elucidate the basis of marked interspecific differences. In trout, plasma catecholamine levels were unchanged when PWO2 remained above 50 Torr but increased markedly when PWO2 was lowered below this value; the predominant catecholamine released into the circulation was epinephrine. In eel, there was no such obvious PWO2 threshold for catecholamine release although plasma levels were consistently elevated above baseline only at PWO2 less than 35 Torr. The magnitude of the catecholamine release in eel was approximately an order of magnitude less than in trout. Unlike in trout, there was no increase in the plasma epinephrine-to-norepinephrine concentration ratio. During hypoxia, the relationship between arterial blood PO2 (PaO2) and PWO2 was similar in both species and thus could not explain the differences in the PWO2 thresholds for catecholamine release. In trout, the calculated PaO2 thresholds for catecholamine release were 25.3 (epinephrine) and 20.5 Torr (norepinephrine) whereas in eel the corresponding values were 12.5 and 11.6 Torr, respectively. These PaO2 thresholds were in good agreement with the in vivo values for PaO2 at half-maximal hemoglobin (Hb)-O2 saturation (P50) for trout and eel blood of 22.9 and 11.1 Torr, respectively. Thus both species displayed essentially equivalent catecholamine release thresholds when expressed in terms of arterial blood O2 content corresponding to approximately 45-60% Hb-O2 saturation.

Animals↗
PubMed1996

Chemoreceptor nerve excitation may not be proportional to catecholamine secretion.

Enhanced catecholamine secretion from the carotid body glomus cells is hypothesized to play an essential role in mediating the peripheral chemoreceptor response to hypoxia. To test aspects of this hypothesis, the relationship between catecholamine secretion and nerve activity was examined during repetitive hypoxia stimuli and after catecholamine depletion with reserpine. Single-fiber afferent serve activity was measured along with an estimate of free tissue catecholamine by using Nafion-coated carbon-fiber microelectrodes placed in rat carotid bodies in vitro. Baseline and stimulated nerve and catecholamine levels were quantified during repetitive stimulation (anoxia of 1-min duration; PO2 = 0 Torr at nadir, repeated each 200 s). Peak stimulated catecholamine progressively decreased from 26.4 +/- 2.6 microM for the first stimulus to 7.5 +/- 0.9 microM for the fifth stimulus (n = 15), but peak nerve activity was much less affected (23.0 +/- 1.9 Hz, first trial; 19.9 +/- 1.4 Hz, fifth trial). An exposure to moderate hypoxia (approximately 80 Torr) before the repetitive anoxia stimuli produced catecholamine levels comparable to those obtained during repetitive anoxia, but peak nerve activity was significantly less (22.5 +/- 3.4 vs. 12.7 +/- 2.1 Hz). Pretreatment with reserpine (1 mg/100 g) resulted in a large reduction in the average hypoxia-induced catecholamine response (1.4 +/- 0.3 microM, n = 9), but peak nerve activity was not different from nontreated controls. These results demonstrate an independence between carotid body catecholamine secretion and nerve activity, suggesting that nerve excitation is, at least, partially mediated through pathways independent of granule secretion.

Animals↗
PubMed1988

Sodium depletion increases platelet and plasma catecholamines in hypertensive men.

The catecholamine content in blood platelets is considerably higher than that in plasma, and platelet catecholamines must be taken up from plasma, since blood platelets lack enzymes for catecholamine synthesis. However, it is unknown whether platelets take up and store catecholamines during physiological in vivo increments in plasma catecholamines. Previously untreated 50-year-old men (n = 17) with mild to moderate essential hypertension were given a low sodium diet for 2 weeks. Urinary excretion of sodium decreased from 201 +/- 11 (SE) to 24 +/- 5 and 19 +/- 4 mmol/24 hr after 1 and 2 weeks, respectively. During the first week, the blood platelet concentration of norepinephrine increased from 27.2 +/- 2.9 to 39.6 +/- 4.7 pg/mg (p less than 0.005) and venous plasma norepinephrine increased from 3.7 +/- 0.4 to 5.6 +/- 0.5 pg/ml (p less than 0.005), and venous plasma dopamine increased from 26 +/- 4 to 41 +/- 5 pg/ml (p less than 0.05). During the second week, both plasma and platelet norepinephrine and dopamine remained elevated. Platelet epinephrine showed a small increase from baseline to the second week (p less than 0.05), but no concomitant increase in plasma epinephrine occurred. Thus, sodium depletion increases both platelet and plasma catecholamines and blood platelets may take up catecholamines in vivo. Platelet catecholamine content may be an integrated measure of plasma catecholamine concentrations during variations caused by sodium depletion.

Blood Platelets↗
PubMed2002

Angiotensin II type 2 receptor counter-regulates type 1 receptor in catecholamine synthesis in cultured porcine adrenal medullary chromaffin cells.

We previously showed that CGP 42112 (an angiotensin type 2 [AT(2)] agonist) markedly reduces catecholamine biosynthesis by decreasing cGMP production mediated by AT(2), a subtype of Ang II receptor that is dominantly expressed in cultured porcine chromaffin cells. To elucidate the relationship of the 2 types of Ang II receptors, angiotensin type 1 (AT(1)) and AT(2), in the synthesis of catecholamine in adrenal medullary cells, we have examined the effect of Ang II plus CV-11974 (an AT(1) antagonist that selectively simulates AT(2) stimulation) and the effect of Ang II plus PD 123319 (an AT(2) antagonist that selectively simulates AT(1) stimulation) on catecholamine synthesis. We found that Ang II reduced cGMP production via AT(2), in a similar manner to that found with CGP 42112. Stimulation of AT(1) significantly upregulated protein kinase C activity. Tyrosine hydroxylase (TH) is a rate-limiting enzyme involved in the biosynthesis of catecholamine, and this catecholamine synthesis depends both on TH enzyme activity and on the levels of TH protein after TH gene transcription. We found that AT(2) stimulation significantly inhibited TH enzyme activity, whereas AT(1) stimulation significantly upregulated TH enzyme activity. The stimulatory effect of AT(1) was completely inhibited by Ro-32-0432 (a protein kinase C inhibitor) and PD 98059 (a MAP kinase kinase-1 [MEK-1] inhibitor). Pretreatment of cells with either 8-Br-cGMP (a membrane-permeable cGMP analog) or Zaprinast (a phosphodiesterase inhibitor) abolished the inhibitory effect of AT(2) on TH enzyme activity, indicating that the stimulatory effect of AT(2) may be mediated through a reduction in cGMP concentration. Similar to the effect on TH enzyme activity, AT(2) stimulation significantly reduced TH mRNA and protein levels and net catecholamine content below basal levels, whereas AT(1) stimulation increased them. We confirmed these findings by gel mobility shift assay. Our results show that stimulation of AT(2) reduces catecholamine biosynthesis via a decrease in cGMP levels. In contrast, stimulation of AT(1) stimulates catecholamine biosynthesis through activation of PKC. Thus, we conclude that AT(1) and AT(2) have counter-regulatory roles in the synthesis of catecholamine in adrenal medullary chromaffin cells.

Adrenal Medulla↗
PubMed1999

Influence of infused catecholamines on the pharmacokinetics of cocaine and benzoylecgonine formation after bolus dose or continuous cocaine administration in the rat.

The purpose of this study was to determine whether a catecholamine infusion administered to simulate a stress state could alter the pharmacokinetics of administered cocaine and effect the formation of benzoylecgonine, its major metabolite, in the rat. In a previous investigation we determined that catecholamine infusion enhanced the toxicity of continuous cocaine infusion by reducing the time before the onset of convulsions and respiratory arrest. We postulated that this enhanced toxicity was an effect of catecholamines on the pharmacokinetics of cocaine. To test this hypothesis we studied plasma cocaine and benzoylecgonine disposition after intravenous bolus administration of cocaine (5 mg kg(-1)) to 19 male Sprague-Dawley rats and to 10 rats which received an initial loading-dose cocaine infusion of 1 mg kg(-1) min(-1) (for 5 min) followed by continuous infusion of 100 microg kg(-1) min(-1). Rats in both studies randomly received either continuous catecholamine infusion comprising adrenaline (7.25 microg mL(-1)), noradrenaline (4.4 microg mL(-1)) and dopamine (8.0 microg mL(-1)) or saline, administered at a similar rate. Bolus dose cocaine administration, simultaneously with catecholamine infusion, resulted in significantly higher Cmax levels for cocaine (3.8 compared with 2.5 microg mL(-1)) and lower distribution half-lives (3.3 compared with 5.9 min) and central compartment volumes of distribution (1.5 compared with 2.1 L kg(-1)) compared with saline infusion. Benzoylecgonine formation was significantly reduced in rats receiving catecholamines whereas the elimination half-lives (26.3 compared with 25.0 min) and systemic clearances (146 compared with 146 mL kg(-1) min(-1)) were not different. Continuous cocaine infusion (after an initial loading infusion) resulted in the doubling of plasma cocaine levels in rats receiving catecholamines compared with the control group. These data indicate that elevated plasma catecholamines have significant effects on cocaine pharmacokinetics. This might serve to explain the enhanced toxicity from concomitant cocaine and catecholamine infusion demonstrated in previous experiments.

Animals↗
PubMed2006

The interactive effects of hypoxia and nitric oxide on catecholamine secretion in rainbow trout (Oncorhynchus mykiss).

Experiments were performed to test the hypothesis that exposure of rainbow trout to repetitive hypoxia would result in a decreased capacity of chromaffin cells to secrete catecholamines owing to increased production of nitric oxide (NO), a potent inhibitor of catecholamine secretion. A partial sequence of trout neuronal nitric oxide synthase (nNOS) was cloned and its mRNA was found to be present in the posterior cardinal vein (PCV), the predominant site of chromaffin cells in trout. Using heterologous antibodies, nNOS and endothelial NOS (eNOS) were localized in close proximity to the chromaffin cells of the PCV. Exposure of trout to acute hypoxia (5.33 kPa for 30 min) in vivo resulted in significant increases in plasma catecholamine and NO levels. However, after 4 days of twice-daily exposures to hypoxia, the elevation of plasma catecholamine levels during hypoxia was markedly reduced. Associated with the reduction in plasma catecholamine levels during acute hypoxia was a marked increase in basal and hypoxia-evoked circulating levels of NO that became apparent after 2-4 days of repetitive hypoxia. The capacity of the chromaffin cells of the hypoxia-exposed fish to secrete catecholamine was assessed by electrical stimulation of an in situ saline-perfused PCV preparation. Compared with control (normoxic) fish, the PCV preparations derived from fish exposed to repeated hypoxia displayed a significant reduction in electrically evoked catecholamine secretion that was concomitant with a marked increased in NO production. This additional rise in NO secretion in preparations derived from hypoxic fish was prevented after adding NOS inhibitors to the perfusate; concomitantly, the reduction in catecholamine secretion was prevented. The increased production of NO during hypoxia in vivo and during electrical stimulation in situ was consistent with significant elevations of nNOS mRNA and protein; eNOS protein was unaffected. These results suggest that the reduced capacity of trout chromaffin cells to secrete catecholamines after repeated hypoxia reflects an increase in the expression of nNOS and a subsequent increase in NO production during chromaffin-cell activation.

Animals↗
PubMed1996

Inappropriate secretion of umbilical plasma catecholamines in preterm compared to term neonates.

To investigate the gestation and stimulus related catecholamine secretion and degradation at birth free and sulfoconjugated adrenaline, noradrenaline and dopamine were analysed in the umbilical artery and vein of 35 preterm and 75 term neonates. A highly sensitive radioenzymatic assay was used for the determination of free catecholamine levels, sulfoconjugated catecholamines were analysed after addition of 25 mU arylsulfatase type VI. Levels of free catecholamines were significantly lower in preterm as compared to term newborns. Hereby, adrenaline levels significantly correlated with the gestational age, birth weight, and birth length. Sulfoconjugated catecholamine levels were similarly lower, but only sulfoconjugated noradrenaline reached differences of statistical significance. The placental extraction rate of adrenaline and noradrenaline was significantly lower in preterm as compared to term neonates. Only in term but not in preterm neonates, arterial pH- and pCO2-levels significantly correlated with arterial plasma catecholamine levels. Therefore, lower catecholamine levels in preterm compared to term neonates result from lower secretion of catecholamines rather than increased degradation and may contribute to their frequent surfactant deficiency. In addition, the inadequate and diminished catecholamine secretion of preterm neonates may play a significant part in their postnatal adaptation problems like hypoglycaemia, hypothermia and occurrence of wet lungs.

Apgar Score↗
PubMed1998

Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas.

OBJECTIVE: To understand the molecular mechanisms by which catecholamine synthesis is controlled in pheochromocytomas--tumors that synthesize and release catecholamines, which are related to various clinical manifestations of the condition. METHODS: We measured the concentrations of mRNA coding for the catecholamine-synthesizing enzymes tyrosine hydroxylase, aromatic L-amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyl transferase (PNMT) and for the catecholamine contents in 12 pheochromocytomas and 12 normal adrenal medullas. RESULTS: The mean content of total catecholamine and the beta-actin mRNA expression in the pheochromocytomas were almost the same as those in the normal adrenal medullas. However, the tyrosine hydroxylase, AADC and DBH mRNA concentrations in the pheochromocytomas were greater than those of the normal adrenal medullas. Conversely, the PNMT mRNA concentration in the pheochromocytomas was lower than that in the normal adrenal medullas. These differences are responsible for the difference in the proportions of catecholamines between pheochromocytomas and normal adrenal medullas. The constitutive expression of the catecholamine-synthesizing enzyme mRNAs varied in magnitude among the pheochromocytomas, and the tyrosine hydroxylase mRNA expressions correlated with the contents of total catecholamine in the tumors (r=0.964, P<0.0001). CONCLUSIONS: These findings indicate that catecholamine production in pheochromocytomas is primarily controlled by the level of gene expression.

Adrenal Gland Neoplasms↗
PubMed2006

Catecholamines: physiological immunomodulators during health and illness.

The existence of an immune-endocrine interaction has been reported and the modulatory effects of the natural occurring catecholamines epinephrine, norepinephrine and dopamine as well as of pharmaceutically generated catecholamines like dopexamine on a wide variety of immune functions were demonstrated. Furthermore, it was noticed that these effects are mediated by specific adrenergic and dopaminergic receptors expressed on the surface of immunological target cells. At first, the adrenergic immunomodulation was predominantly investigated in healthy volunteers and profound immunomodulatory effects were reported for endogenously released and exogenously administered catecholamines. To further elucidate the physiological significance of these interactions, investigators tried to reveal the importance of the catecholaminergic modulation of the immune system under pathological conditions like hemorrhagic shock and systemic inflammation, since catecholamines and adrenergic antagonists are frequently used drugs in the treatment of the critically ill. Furthermore, the interaction between catecholamines and the immune system is supposed to be an important factor in the development of autoimmune diseases and may influence their progress. In addition to the effects of peripheral circulating catecholamines, it was demonstrated that catecholamines that are released within the central nervous system may profoundly influence the activity of the peripheral immune system. Starting with a short historical overview over the immunomodulatory effects of blood catecholamines under good health conditions during critical illness and during autoimmune disease will be reviewed and the immunomodulatory effects of centrally released catecholamines will be discussed.

Animals↗
PubMed1998

Ultrastructural and biochemical characterization of catecholamine release mechanisms in cultured human pheochromocytoma cells.

OBJECTIVE: To characterize ultrastructurally and biochemically catecholamine release mechanisms of cultured human pheochromocytoma cells in the basal and stimulated states. METHODS: The cultured pheochromocytoma cells were prepared from human adrenal pheochromocytoma tumors. Biochemical determinations of catecholamine secretion from the cultured cells were carried out in the basal and stimulated states. Transmission electron microscopy was used to observe the modes of catecholamine release from the cells without and with stimulation by depolarization of the cells with the administration of 50 mmol/L KCl. RESULTS: Biochemical determinations consistently showed spontaneous secretion of catecholamines from the cultured cells in the basal state without stimulation. Catecholamine release in a calcium-dependent manner could be enhanced in the cells in response to high extracellular potassium concentration. A series of electron microscopic observations of the cultured cells consistently disclosed the classical exocytotic profiles on the cell surface in the basal state. In addition to abundant increase in the number of classical single exocytosis, compound exocytosis was frequently observed in the stimulated cells. Furthermore, other modes of catecholamine release mechanism involving the formation of pseudopodial and/or tubule-like structures, which were different from classical exocytosis, were often present in the intensely stimulation cells. CONCLUSIONS: Based on the biochemical and electron microscopic findings, we concluded: (1) classical single exocytosis is considered to be a primary mechanism responsible for spontaneous secretion of catecholamines from the cells in the basal state; (2) compound exocytosis is an essential mechanism for extruding large amounts of catecholamines in the stimulated cells; and (3) other modes of catecholamine release mechanism may operate in the cells in response to intense stimulation. These morphological data may be helpful in explanation of biochemical variability and extreme diversity of clinical manifestations in patients with pheochromocytoma tumor.

Adrenal Gland Neoplasms↗
PubMed1975

A comparison of the effects of morphine and forced running upon the incorporation of 14-C-tyrosine into 14-C-catecholamines in mouse brain, heart and spleen.

Morphine increases both the locomotor activity of mice and the incorporation of 14-C-tyrosine into 14-C-catecholamines in the mouse brain. To determine whether a relationship exists between increases in locomotor activity and increases in catecholamine synthesis, mice were treated with either morphine (100 mg/kg i.p.) or saline and were forced to run on a treadmill (5.4 m/min). When mice were given saline and forced to run, incorporation of 14-C-tyrosine into 14-C-catecholamines was increased over control values in the heart and spleen but unchanged in the brain. When mice were given morphine, but not forced to run, the incorporation of 14-C-tyrosine into 14-C-catecholamines was increased over control values in the brain but unchanged in the heart and spleen. Morphine decreased the catecholamine content of the mouse brain but not of the heart or spleen. Forced running did not change the catecholamine content of any tissue. The differences between the effects of morphine and forced increases in locomotor activity upon the incorporation of 14-C-tyrosine into 14-C-catecholamines and upon the catecholamine content in various tissues of the mouse indicate that the effects of morphine on catecholamine synthesis are not the result of changes in locomotor activity.

Animals↗
PubMed2003

Intracellular patch electrochemistry: regulation of cytosolic catecholamines in chromaffin cells.

Alterations in the cytosolic pool directly affect neurotransmitter synthesis and release and are suggested to be key factors in various neurodegenerative disorders. Although this cytosolic pool is the most metabolically active, it is miniscule compared with the amount of vesicular transmitter and has never been quantified separately. Here, we introduce intracellular patch electrochemistry (IPE), a technique that for the first time provides direct measurements of cytosolic oxidizable molecules in single mammalian cells. In amperometric mode, IPE detects total catechols, whereas in cyclic voltammetric mode, it preferentially measures catecholamines. In cultured chromaffin cells, the total cytosolic catechol concentration was 50-500 microm, of which approximately 10% were catecholamines. Reserpine, a vesicular monoamine transporter inhibitor, had no effect on the catecholamine pool but increased total catechols by fourfold to fivefold. Combined with pargyline, a monoamine oxidase inhibitor, reserpine increased catecholamine levels in the cytosol by approximately sixfold. Amphetamine induced a transient approximately fivefold accumulation of cytosolic catecholamines and a slow increase of total catechols. In cells incubated with 3,4-dihydroxy-L-phenylalanine (L-DOPA), catecholamines increased by approximately 2.5-fold and total catechols increased by approximately fourfold. Cytosolic catecholamines returned to control levels <or=10 min after L-DOPA withdrawal, whereas total catechols remained approximately twofold elevated even after a 1.5 hr incubation in L-DOPA-free media. Our data indicate that cytosolic catecholamines are strictly maintained at a defined level, and drug-induced increases in their concentrations lead to the accumulation of other catecholamine derivatives, such as DOPAC and 3,4-dihydroxyphenylethyleneglycol. These derivatives reside in the cytosol for hours after treatment and may be an underlying cause of drug-related cytotoxicity.

Adrenergic Uptake Inhibitors↗
PubMed1992

Beta-adrenergic receptors: astrocytic localization in the adult visual cortex and their relation to catecholamine axon terminals as revealed by electron microscopic immunocytochemistry.

It has long been recognized that noradrenaline, the most abundant catecholamine within the visual cortex, plays important roles in modulating the sensitivity of cortical neurons to visual stimuli. However, whether or not these noradrenaline effects are confined to a discrete synaptic specialization or mediated by diffuse modulation of a group of synapses has remained an issue open for debate. The aim of this study was to examine the cellular basis for noradrenaline action within the visual cortex of adult rats and cats. To this end, I used electron microscopic immunocytochemistry to examine the relationship between (1) catecholamine axon terminals and beta-adrenergic receptors (beta AR), which, together, may define the effective sphere of noradrenaline modulation; and then (2) these putative sites for catecholamine modulation and axospinous asymmetric junctions where excitatory neurotransmission is likely to dominate. Antibodies against beta AR were used at light and electron microscopic levels on the visual cortex of rat and cat. Rat visual cortex was also labeled simultaneously for beta AR and the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), to determine the ultrastructural relationships between catecholamine terminals and beta AR. Immunoperoxidase labeling revealed that beta AR404, a polyclonal antibody directed against the C-terminal tail of hamster lung beta AR (beta 2-type), recognized astrocytic processes predominantly. In contrast, beta AR248, a polyclonal antibody directed against the third cytoplasmic loop, recognized neuronal perikarya as observed in previous studies. Dual labeling for beta AR404 and TH revealed that catecholamine axon terminals that contained numerous vesicles formed direct contacts with astrocytic processes exhibiting beta AR404 immunoreactivity. However, some catecholamine axon terminals that lacked dense clusters of vesicles were positioned away from beta AR404-immunoreactive astrocytes. Frequently, beta AR-immunoreactive astrocytic processes surrounded asymmetric axospinous junctions while also contacting catecholamine axon terminals. These observations support the possibility that, through activation of astrocytic beta AR, noradrenaline modulates astrocytic uptake mechanism for excitatory amino acids, such as L-glutamate. Astrocytic beta AR might also define the effective sphere of catecholamine modulation through alterations in the morphology of distal astrocytic processes and the permeability of gap junctions formed between astrocytes.

Animals↗
PubMed1991

Role of protein kinase C in catecholamine secretion from digitonin-permeabilized bovine adrenal medullary cells.

The effects of staurosporine and K-252a, potent inhibitors of protein kinases, and 12-O-tetradecanoylphorbol-13-acetate (TPA) on catecholamine secretion and protein phosphorylation in digitonin-permeabilized bovine adrenal medullary cells were investigated. Staurosporine and K-252a (0.01-10 microM) did not cause large changes in catecholamine secretion evoked by Ca2+ in digitonin-permeabilized cells whereas these compounds strongly prevented TPA-induced enhancement of catecholamine secretion in a concentration-dependent manner. Incubation of digitonin-permeabilized cells with [gamma-32P]ATP resulted in 32Pi incorporation into a large number of proteins, detected as several major bands and darkened background in autoradiograms. Ca2+ and TPA increased phosphorylation of these proteins. Staurosporine and K-252a markedly inhibited Ca(2+)-induced and TPA-induced increases in protein phosphorylation as well as basal (0 Ca2+) protein phosphorylation in digitonin-permeabilized cells. Long term treatment (24 h) of adrenal medullary cells with 1 microM TPA markedly decreased total cellular protein kinase C activity to about 5.3% of control. Pretreatment of the cells with 1 microM TPA strongly inhibited the TPA-induced enhancement of catecholamine secretion whereas it did not cause large changes in total cellular catecholamine amounts, Ca(2+)-induced catecholamine secretion, and cAMP-induced enhancement of catecholamine secretion from digitonin-permeabilized cells. From these results we conclude that protein kinase C plays a modulatory role in catecholamine secretion rather than being essential for initiating catecholamine secretion.

Adrenal Medulla↗