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PubMed1988

Effects of protonophores on the synthesis of catecholamines and the intracellular pH in cultured bovine adrenal medullary cells.

The protonophores carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and carbonyl cyanide m-chlorophenylhydrazone (CCCP) stimulated the synthesis of 14C-catecholamines from [14C]tyrosine in cultured bovine adrenal medullary cells. The stimulatory effect of CCCP but not of FCCP was partially dependent on extracellular Ca2+. CCCP but not FCCP increased the influx of 45Ca2+ to the cells. When cells were incubated with either CCCP or FCCP (0.01-0.2 microgram/ml), the intracellular pH fell from 7.2 to 6.3-6.5 and catecholamine synthesis increased. Tyrosine hydroxylase activity in a soluble fraction prepared from cultured adrenal medullary cells was measured after incubation of the cells with FCCP or CCCP. Although FCCP did not affect the activity of the enzyme, CCCP caused a stable activation of it which was dependent on extracellular Ca2+. Since the optimal pH of soluble tyrosine hydroxylase is around 6.0 in adrenal medullary cells, FCCP may increase the synthesis of catecholamines by shifting the intracellular pH toward it. In addition to this mechanism, CCCP may enhance the synthesis of catecholamines by a Ca2+-dependent mechanism.

Adrenal Medulla↗
PubMed1988

Noncholinergic transmitter(s) maintains secretion of catecholamines from rat adrenal medulla for several hours of continuous stimulation of splanchnic neurons.

The effect of continuous stimulation of splanchnic nerves at 1, 3, and 10 Hz on the secretion of catecholamines from the isolated rat adrenal gland was examined. Secretion evoked at 10 Hz declined over 60% in 1 h, and by the end of 4 h the secretion was only 10% of the initial value. The secretion evoked at 3 Hz was unchanged in the first hour, but showed a gradual decline in subsequent hours. In contrast, secretion evoked at 1 Hz was well maintained for several hours. Even after 6 h of continuous stimulation, the decline was only about 35%. Atropine plus hexamethonium reduced the secretion evoked at 10 Hz by over 80%, but that evoked at 1 Hz was reduced by about 35%; addition of naloxone reduced it to 75%. When the secretion declined to very low levels after continuous stimulation at 10 Hz for 100 min, a change in frequency to 3 Hz or 1 Hz caused a sharp rebound in the secretory response. Returning the frequency back to 10 Hz led to a sharp drop in the secretion, whereas reducing the frequency to 1 or 3 Hz once again increased the secretion. The rebound in the secretory response after switchover of frequencies was observed in the presence of atropine plus hexamethonium, but was abolished by naloxone. Extensive stimulations, which caused large amounts of catecholamine secretions at each frequency, were not associated with any loss in tissue catecholamine contents. The major conclusion is that secretion of catecholamines is maintained uninterrupted for several hours when splanchnic nerves are stimulated at low frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1992

Diadenosine tetraphosphate is co-released with ATP and catecholamines from bovine adrenal medulla.

Secretion of adenosine(5')tetraphospho(5')adenosine (Ap4A) and ATP from perfused bovine adrenal glands stimulated with acetylcholine or elevated potassium levels was measured and compared with that of catecholamines. We have found a close correlation between the release of Ap4A and catecholamines elicited with all the secretagogues used in the presence of either Ca2+ or Ba2+, suggesting co-release of both constituents from the chromaffin granules. By contrast, ATP secretion, as measured with luciferase, showed a significantly different time course regardless of the secretagogue used. ATP secretion consistently decreased after 1-2 min of stimulation at a time when Ap4A and catecholamine secretions were still increasing. Measures of degradation of injected [3H]ATP to the gland during stimulation showed little difference in the level of uptake or decomposition of ATP throughout the pulse. However, a reexamination of ATP secretion by monitoring its products of degradation (AMP, adenosine, and inosine) by HPLC techniques showed that Ap4A, ATP, and catecholamines are indeed secreted in parallel from the perfused adrenal gland.

Acetylcholine↗
PubMed1993

Histamine evokes greater increases in phosphatidylinositol metabolism and catecholamine secretion in epinephrine-containing than in norepinephrine-containing chromaffin cells.

Chromaffin cells have H1 histamine receptors. Histamine, acting at these receptors, increases the metabolism of inositol-containing phospholipids and stimulates catecholamine secretion from chromaffin cells. We have investigated the effects of histamine and other agents on the accumulation of inositol monophosphate (InsP1) and catecholamine secretion in purified cultures of norepinephrine-containing and epinephrine-containing bovine chromaffin cells. Histamine-stimulated InsP1 accumulation in epinephrine cells was three times greater than that in norepinephrine cells. In contrast, bradykinin caused roughly equivalent increases in InsP1 accumulation in the two chromaffin cell subtypes. Histamine-stimulated catecholamine secretion was also greater in epinephrine cells than in norepinephrine cells, whereas high K+, bradykinin, phorbol 12,13-dibutyrate, and angiotensin II all caused greater secretion from norepinephrine cells than from epinephrine cells. The density of H1 receptors in epinephrine cells was approximately three times greater than that in norepinephrine cells. The greater density of H1 receptors on epinephrine cells may account for the greater effects of histamine on InsP1 accumulation and catecholamine secretion in these cells.

Adrenal Glands↗
PubMed1993

A toxin fraction (FTX) from the funnel-web spider poison inhibits dihydropyridine-insensitive Ca2+ channels coupled to catecholamine release in bovine adrenal chromaffin cells.

In adrenal chromaffin cells, depolarization-evoked Ca2+ influx and catecholamine release are partially blocked by blockers of L-type voltage-sensitive Ca2+ channels. We have now evaluated the sensitivity of the dihydropyridine-resistant components of Ca2+ influx and catecholamine release to a toxin fraction (FTX) from the funnel-web spider poison, which is known to block P-type channels in mammalian neurons. FTX (1:4,000 dilution, with respect to the original fraction) inhibited K(+)-depolarization-induced Ca2+ influx by 50%, as monitored with fura-2, whereas nitrendipine (0.1-1 microM) and FTX (3:3), a synthetic FTX analogue (1 mM), blocked the [Ca2+]i transients by 35 and 30%, respectively. When tested together, FTX and nitrendipine reduced the [Ca2+]i transients by 70%. FTX or nitrendipine reduced adrenaline and noradrenaline release by approximately 80 and 70%, respectively, but both substances together abolished the K(+)-evoked catecholamine release, as measured by HPLC. The omega-conotoxin GVIA (0.5 microM) was without effect on K(+)-stimulated 45Ca2+ uptake. Our results indicate that FTX blocks dihydropyridine- and omega-conotoxin-insensitive Ca2+ channels that, together with L-type voltage-sensitive Ca2+ channels, are coupled to catecholamine release.

Adrenal Glands↗
PubMed1989

Effect of apomorphine on adrenal medullary catecholamine levels.

The effects of the dopamine receptor agonist, apomorphine, on the total catecholamine content of the adrenal medulla were studied in normotensive rats. Apomorphine (3, 15, 30 mg/kg SC) induced a dose-dependent decrease in catecholamine content of the adrenal gland. The action of apomorphine was suppressed by previous treatment with the non specific dopamine receptor antagonist, haloperidol (9 mg/kg IP), or the D2 antagonist domperidone (2 mg/kg IP), but not by the D1 antagonist SCH 23390 (1 mg/kg IP). The apomorphine-induced decrease in adrenal catecholamine concentration was suppressed by denervation of the adrenal medulla, i.e. unilateral section of splanchnic fibers performed 5 days before. These results show that, under our experimental conditions, the effect of apomorphine is due to the activation of D2 dopamine receptors probably located on splanchnic nerve endings and suggest the existence of a peripheral D2 dopaminergic system which modulates adrenal medullary catecholamine content.

Adrenal Medulla↗
PubMed1995

Differential activation of beta 1-, beta 2- and beta 3-adrenoceptors by catecholamines in white and brown adipocytes.

This review summarizes the experiments performed by various groups to determine how the activation of the different beta-adrenoceptors (beta-ARs) is ordinated when they are present in the same fat cell and involved in the same biological event. When expressed after the transfection of their genes in Chinese hamster ovary cell (CHO cells), beta 1- and beta 2-ARs present a higher affinity for catecholamines than beta 3-ARs. In vitro, the lipolytic effect induced by low concentrations of catecholamines in dog and rat white fat cells is due to the selective activation of beta 1- and/or beta 2-ARs. Higher concentrations only are able to activate beta 3-ARs. Similar results have been obtained in rat brown adipocytes. On the other hand, the lipolytic effect of catecholamines in human and primate adipocytes does not involve a beta 3-AR component whatever the concentration used. In vivo experiments in the dog have also shown that lipomobilization induced by low doses of isoprenaline only involved beta 1- and beta 2-AR activation, this effect being blocked by beta 1-/beta 2-antagonist pretreatment. However, in the same blockade conditions, perfusion of a 10-fold higher dose of isoprenaline revealed a beta 3-AR contribution in the lipomobilizing effect. These data showed that brown and white adipocyte beta 3-ARs possess a lower affinity for catecholamines than beta 1- and beta 2-ARs and are only recruited by high concentrations of the amines.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗
PubMed1995

Propranolol therapy in experimental heart failure in rabbits improves cardiac response to catecholamines without beta-adrenoceptor up-regulation.

Beta-blockade has been shown to improve cardiac response to catecholamines in heart failure but cellular mechanisms of the improvement are unknown. The effect on left ventricular function of a 14 day propranolol treatment was studied in seven treated and eight non-treated rabbits with experimental heart failure. All animals were subjected to a volume (aortic insufficiency) plus pressure (aortic constriction) overload and were instrumented with a left ventricular catheter and ultrasonic crystals measuring anteroposterior left ventricular diameter. Beta-adrenoceptors were measured using 125I-Cyanopindolol in crude membranes. With isoproterenol, the heart rate was slower in treated rabbits than in non-treated rabbits (p < 0.005) and isoproterenol increased more systolic diameter shortening in treated than in non-treated rabbits (p < 0.05). With norepinephrine, for matched pressures, % delta D increased in the treated group but it did not change in the non-treated group. This improvement of ventricular function was due, in a large part, to an increased diastolic response to norepinephrine: end-diastolic diameter increased in the treated group but not in the non-treated group. In contrast with the improved ventricular response to catecholamines, beta-adrenergic receptor density in the treated group was identical to that of the non-treated group (27.8 fmoles/mg/proteins) and was significantly lower than that of normal rabbits (58.2 fmoles/mg, p < 0.01). The improvement of ventricular response to catecholamines appears to be due to a myocardial protection by propranolol against the toxic effect of catecholamines in heart failure and not, at least in this model, to an up-regulation of beta-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1969

Factors involved in maintenance of cardiac catecholamine content: relative importance of synthesis and re-uptake.

1. When animals were exposed to a temperature of 4 degrees C for 6 hr, endogenous catecholamines remained unaltered or reduced slightly depending upon the strain of rats used. In contrast, labelled noradrenaline declined rapidly, but the decline was inhibited when animals were pretreated with monoamine oxidase inhibitors.2. Increased sympathetic nervous activity associated with cold resulted in a four-fold increase in rate of synthesis of noradrenaline.3. Reduction in endogenous and labelled catecholamine levels associated with cold was exaggerated by pretreatment with cocaine, imipramine or phenoxybenzamine-drugs known to inhibit the uptake of noradrenaline into the nerve terminal.4. Cocaine and imipramine in higher doses inhibited the release of both endogenous and labelled noradrenaline, suggesting a dual action: in small doses they increased the depletion of catecholamines by blocking the reincorporation, while in higher doses they inhibited the release of noradrenaline.5. It is concluded that, under normal conditions, the re-uptake mechanism may not play a significant role in the maintenance of normal cardiac catecholamine levels and that such levels are maintained by synthesis alone. However, when the heart is subjected to high impulse nerve activity, synthesis is not sufficiently accelerated to compensate for impulse-induced massive release and may require the support of an additional mechanism, such as the partial reincorporation of released transmitter. In fact, the re-uptake mechanism is enhanced during high impulse activity.

Adrenal Medulla↗
PubMed1970

Effects of intraventricular 2,4,5-trihydroxyphenylethylamine (6-hydroxydopamine) on rat behaviour and brain catecholamine metabolism.

1. 6-Hydroxydopamine (200 mug injected intraventricularly) caused depletion of noradrenaline from all regions of rat brain within 2 h after injection but depletion of dopamine in the brain was observed only from 2 days after injection. Both catecholamines remained depleted for more than 32 days.2. Rats treated with intraventricular 6-hydroxydopamine were sedated and lethargic, with reduced spontaneous and exploratory activity, for periods of up to 8 days after injection. Conditioned avoidance responding was abolished or reduced for a similar period.3. Intraventricular 6-hydroxydopamine caused a prolonged reduction in the amount of labelled catecholamines in store 4 h following an intraventricular injection of (3)H-dopamine. During the first 6 h after 6-hydroxydopamine injection, there was a marked increase in neutral and acid metabolites from the labelled catecholamines.4. A comparison of the behavioural and biochemical effects of intraventricular 6-hydroxydopamine and reserpine suggests that both drugs affect catecholamine storage mechanisms but by different mechanisms. It was not possible from these experiments to correlate behavioural changes with either catecholamine storage or metabolism.

Animals↗
PubMed1981

Liberation of catecholamines from blood platelets.

1 Platelet-rich plasma (PRP) of guinea-pigs with or without reserpine was preincubated either with [(14)C]-5-hydroxytryptamine ([(14)C]-5-HT) plus [(3)H]-dopamine or with [(14)C]-5-HT plus [(3)H]-noradrenaline ([(3)H]-NA). After isolation on two successive dextran gradients the double-labelled platelets were incubated in Tris-buffer in the presence or absence of various drugs. The decrease in radioactivity in the platelets was measured in order to determine the amount of the amine that had been liberated.2 Spontaneous liberation of the labelled amines was more marked in reserpine-treated platelets than in normal ones and somewhat more pronounced for the (3)H-catecholamines than for [(14)C]-5-HT.3 The reserpine-like benzoquinolizine, Ro 4-1284, caused liberation of all three labelled amines in normal but not in reserpine-treated platelets. More [(3)H]-dopamine was liberated than [(14)C]-5-HT and less [(3)H]-NA.4 The arylalkylamines, tyramine and p-chloromethamphetamine (PCMA), liberated all three labelled amines from normal platelets, and [(14)C]-5-HT and [(3)H]-dopamine, but not [(3)H]-NA from reserpine-treated ones. In normal platelets dopamine was reduced to a greater extent than [(14)C]-5-HT and [(3)H]-NA to a smaller extent, whereas in reserpine-treated platelets [(14)C]-5-HT was more markedly diminished than [(3)H]-dopamine.5 The 5-HT uptake inhibitor, imipramine, had little influence on the spontaneous and drug-induced liberation of [(14)C]-5-HT and [(3)H]-dopamine.6 It is concluded that (3)H-catecholamines like [(14)C]-5-HT are mostly localized in the granular pool of platelets; the three drugs tested liberate [(3)H]-dopamine [(3)H]-NA and [(14)C]-5-HT from the granular pool. Ro 4-1284 does not liberate (3)H-catecholamines and [(14)C]-5-HT from extragranular sites whereas tyramine and PCMA also act on the extragranular pool of [(3)H]-dopamine and [(14)C]-5-HT but not [(3)H]-NA.7 The liberation of catecholamines from platelets differs from that of 5-HT in several respects and platelets are only partly comparable to neurones as far as drug-induced liberation of biogenic amines is concerned.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1981

Potentiation of K+-evoked catecholamine release in the cat adrenal gland treated with ouabain.

1 A vigorous catecholamine secretory response was evoked by small increments (2-10 mM) of the extracellular concentration of K+ ([K+])o) in cat adrenal glands treated with ouabain (10(-4) M), and perfused with Krebs-bicarbonate solution at room temperature. 2 The secretory response depends on [K+]o; increments of [K+]o as small as 2 mM for 2 min evoked a clear secretory response; at 10-17.7 mM K+, the maximal secretory response was observed. In normal glands, not treated with ouabain, no increase of the rate of catecholamine output was observed by raising [K+]o up to 17.7 mM for 2 min. 3 The K+ secretory response was time-dependent, requiring at least 1 min to be initiated; on continued exposure to 10 mM [K+]o, the enhanced response remained for at least 1 h. 4 In low [Na+]o, the K+-secretory response was unchanged. However, in 0-Ca2+, high-Mg2+ solutions, or in the presence of D600, an organic Ca2+ antagonist, it was abolished. 5 The K+-induced secretory response was not altered in the presence of tetrodoxin or tetraethylammonium. 6 It is concluded that ouabain potentiated the catecholamine secretory response to raised [K+]o by increasing the amount of Ca2+ available to the secretory machinery through (a) mobilization of an enhanced pool of membrane-bound Ca2+, (b) activation of membrane Ca2+ inward current; or (c) decrease of intracellular Ca2+ buffering systems. The activation by ouabain of a membrane Na+-Ca2+ exchange system is not involved in this K+-secretory response. It is suggested that the plasma membrane ATPase enzyme system, by changing the affinity of its Ca2+ binding sites, might control the availability of this cation to the secretory machinery and, therefore, modulate catecholamine secretion in the adrenal gland.

Adrenal Glands↗
PubMed1982

Inhibitory actions of catecholamines on electrically induced contractions of the submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus.

1 The submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus was used to study the actions of catecholamines on the twitch responses to electrical stimulation.2 When the preparation was stimulated coaxially (0.1 Hz, 0.5 ms, supramaximal voltage), stable twitch-like contractions were obtained. These were abolished by tetrodotoxin (0.1 muM) and atropine (0.1 muM), potentiated by physostigmine (0.1 muM), and were mediated presumably by stimulation of intramural cholinergic nerves.3 The twitch contractions of the muscularis mucosae were inhibited by catecholamines, in a concentration-dependent manner. The order of potency was isoprenaline > adrenaline > noradrenaline > dopamine.4 The inhibitory actions of noradrenaline (1 muM) and adrenaline (1 muM) were partly reversed by phentolamine (1 muM) or by propranolol (1 muM), and completely abolished by both antagonists together. The inhibitory effect of dopamine (300 muM) was largely reversed by phentolamine (1 muM), but not by propranolol (1 muM), while the inhibitory action of isoprenaline was competitively antagonized only by propranolol (pA(2) of 7.6).5 The contraction of the muscularis mucosae to exogenously applied acetylcholine (ACh, 20 nM) which was comparable in magnitude with that to electrical stimulation was also inhibited by isoprenaline (0.1 muM), adrenaline (1 muM) and noradrenaline (1 muM), but not by dopamine (300 muM). In the presence of propranolol (1 muM), noradrenaline, adrenaline and dopamine potentiated the ACh-induced contraction, while the effect of isoprenaline was mainly antagonized. The potentiating effects were antagonized by further treatment with phentolamine (1 muM).6 Adrenaline, noradrenaline and dopamine but not isoprenaline, produced a weak contraction of the longitudinal muscularis mucosae in the presence of propranolol (3 muM). The contractile responses were completely inhibited by phentolamine (3 muM). Tone in the muscularis mucosae induced by carbachol (3 muM) in the presence of phentolamine (10 muM) was inhibited by catecholamines, in a concentration-dependent manner, an effect that was competitively antagonized by propranolol.7 In the submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus there are three types of adrenoceptor, inhibitory prejunctional alpha-adrenoceptors, excitatory postjunctional alpha-adrenoceptors and inhibitory postjunctional beta-adrenoceptors, and cholinergic neurotransmission is inhibited by catecholamines acting at both prejunctional alpha- and postjunctional beta-adrenoceptors.

Animals↗
PubMed1989

Analysis of the hyperpolarizing effect of catecholamines on canine cardiac Purkinje fibres.

1. The hyperpolarization induced by catecholamines on barium-depolarized (0.2-0.8 mM BaCl) canine cardiac Purkinje fibres, in vitro, was studied by use of conventional microelectrode recordings of transmembrane electrical potentials. 2. Noradrenaline, adrenaline and isoprenaline hyperpolarized Purkinje fibres in a concentration-dependent manner from a threshold concentration around 5 nM. The three catecholamines were shown to be approximately equipotent. Tachyphylaxis was observed when the interval between catecholamine applications was less than 15 min. 3. Atenolol (10 microM) blocked the hyperpolarization reversibly and theophylline (0.5 mM) potentiated it. 4. Tetrodotoxin (5 microM) did not affect the hyperpolarization induced by isoprenaline. Acetylcholine and histamine, up to 10 microM, were not effective in hyperpolarizing Purkinje fibres. 5. Low extracellular potassium concentrations (zero and 1 mM) did not affect the hyperpolarization, but high extracellular potassium concentrations (10-20 mM), markedly reduced the effect of isoprenaline (100 nM). 6. Reduction of the extracellular sodium concentration produced a roughly proportional reduction in the isoprenaline-induced hyperpolarization. The hyperpolarization was reversibly blocked in 34 mM sodium Tris-Tyrode solution. 7. The hyperpolarization was not reduced in Tyrode solution containing 0.6 mM calcium, but was drastically reduced in zero-calcium Tyrode solution. This effect was reversible. 8. Addition of verapamil (5-10 microM) diminished the hyperpolarization, in a concentration-dependent manner. This effect was partially reversed after washing. 9. Ouabain (0.7-1 microM) significantly reduced the isoprenaline-induced hyperpolarization, but 2,4-dinitrophenol (0.2 mM) did not affect it. 10. Caesium chloride (20 mM) abolished the hyperpolarization. The blockade was only partially reversed upon washing. 11. It is suggested that the hyperpolarization induced by a short exposure to catecholamines is mainly due to an increase in potassium permeability (PK). A mechanism involving calciumdependent potassium channels might underlie the increase in PK.

Animals↗
PubMed1993

R56865 inhibits catecholamine release from bovine chromaffin cells by blocking calcium channels.

1. The effects of R56865 (a new class of cardioprotective agent which prevents Na+ and Ca2+ overload in cardiac myocytes) on catecholamine release, whole-cell current through Ca2+ channels (IBa) and cytosolic Ca2+ concentrations, [Ca2+]i, have been studied in bovine chromaffin cells. 2. R56865 caused a time- and concentration-dependent blockade of catecholamine release from superfused cells stimulated intermittently with 5 s pulses of 59 mM K+. After 5 min superfusion, a 3 microM concentration inhibited secretion by 20%; the blockade increased gradually with perfusion time, to reach 85% after 40 min. The IC50 to block secretion after 5 min periods of exposure to increasing concentrations of R56865 was around 3.1 microM. The blocking effects of R56865 were reversible after 5-15 min wash out. In high Ca2+ solution (10 mM Ca2+), the degree of blockade of secretion diminished by 20% in comparison with 1 mM Ca2+. 3. In electroporated cells, R56865 (10 microM) did not modify the secretory response induced by the application of 10 microM free Ca2+. 4. R56865 blocked the peak IBa current in a concentration- and time-dependent manner; its IC50 was very similar to that obtained for secretion (3 microM). The compound not only reduced the size of the peak current but also promoted its inactivation; when the effects of R56865 were measured at the most inactivated part of the current, its IC50 was 1 microM. Both the inactivation and the reduction of the peak currents were reversible upon washing out the drug. 5. In fura-2-loaded single chromaffin cells the basal [Ca2+]i of around 100 nM was elevated to a peak of1.5 microM by the application of a 5 s pulse of 59 mM K+. R56865 (10 microM) did not affect the basal [Ca2+]but blocked by 90% the K+-evoked increase. This effect was fully reversible after 5-10 min of wash out.6. The results are compatible with the idea that R56865 blocks Ca2+ entry into K+-depolarized chromaffin cells by promoting the inactivation of voltage-dependent Ca2+ channels; this would lead to the limitation of the rise in [Ca2+]i and of the release of catecholamines. The restriction of catecholamine release may favour indirectly the known direct beneficial cardioprotective actions of R56865.

Animals↗
PubMed1994

Inhibitory effects of caffeine on secretagogue-induced catecholamine secretion from adrenal chromaffin cells of the guinea-pig.

1. The inhibitory action of caffeine on catecholamine secretion induced by secretagogues was investigated in perfused adrenal glands and dispersed chromaffin cells of the guinea-pig. 2. Caffeine (10 mM) caused a reversible inhibition of catecholamine secretion evoked by acetylcholine (ACh, 50 microM), KCl (56 mM, high K+) and veratridine (100 microM) and that induced by muscarinic receptor activation in the absence of extracellular Ca2+ in perfused adrenal glands. 3. In dispersed chromaffin cells, caffeine caused a dose-dependent inhibition of the secretory responses to 100 microM ACh and veratridine. Forskolin (30 microM), dibutyryl cyclic AMP (1 mM) and 8-bromo cyclic AMP (1 mM) did not mimic the action of caffeine. 4. In the voltage-clamp, whole-cell recording mode (at a holding potential of -60 mV or -70 mV), ACh (100 microM) evoked an inward current, and depolarizing pulses elicited inward Na+, Ca2+ and outward K+ currents. All these responses were partially inhibited by caffeine (20 mM). 5. ACh rapidly increased the intracellular concentration of Ca2+ ([Ca2+]i) in fura-2-loaded cells in either the presence or the absence of external Ca2+, though its magnitude was decreased by about 50% in Ca(2+)-free conditions. Caffeine (20 mM) inhibited these ACh-induced increases in [Ca2+]i. 6. In permeabilized chromaffin cells, caffeine (20 mM) caused an inhibition of catecholamine secretion evoked by Ca2+ (10 microM). 7. These results suggest that caffeine inhibits evoked catecholamine secretion through mechanisms such as the blockade of voltage-dependent Na+ and Ca2+ currents and ACh receptor current, and reduction of the release of intracellularly stored Ca2+ and/or Ca(2+)-sensitivity of the secretory apparatus.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Receptor for catecholamines responding to catechol which potentiates voltage-dependent calcium current in single cells from guinea-pig taenia caeci.

1. Single isolated cells were obtained from the taenia of the guinea-pig's caecum by enzymic digestion and held under voltage clamp. The effects of various catecholamines, sympathomimetics and related compounds were tested for their ability to potentiate the voltage-dependent calcium current (ICa) evoked in these cells by a depolarizing step. 2. ICa was potentiated by up to 60% by isoprenaline, adrenaline, and noradrenaline which were equipotent. The EC50 for isoprenaline was about 40 nM. 3. The racemic mixtures of the optical isomers of isoprenaline, adrenaline, and noradrenaline, and (+)-isoprenaline, were equipotent with the (-)-isomers of these drugs. Dopamine, L-dopa, and catechol were equipotent with these catecholamines. 4. Removal or substitution of one or more of the hydroxy groups of the catechol moiety, as in phenylephrine, salbutamol, procaterol, methoxamine, terbutaline, BRL 37344, ICI 215001 or tyramine substantially reduced efficacy and/or potency. 5. The adrenoceptor blockers propranolol, phentolamine, dihydroergotamine, atenolol, CGP 20712A and ICI 118551, or the dopamine receptor blockers, haloperidol or flupenthixol, did not block the potentiating action of catechol or the catecholamines. 6. The receptor activated by catecholamines to increase ICa we suggest should be called a C-receptor in view of its sensitivity to catechol. It may arise by enzymic modification of a conventional adrenoceptor but its transduction also involves a novel mechanism which might indicate that it is present in the muscle cells before enzyme treatment.

Animals↗
PubMed1988

Alterations in regional catecholamine content and turnover in the male rat brain in response to in utero ethanol exposure.

Fetal ethanol exposure is known to produce CNS abnormalities. The molecular basis for these manifestations observed in animals exposed to ethanol in utero may be explained by changes in regional catecholamine content and turnover. This study was designed to determine changes in catecholamine content and turnover in the cerebral cortex, cerebellum, medial basal hypothalamus, diencephalon, and septal area of male rats exposed to ethanol pre- and postnatally. Pregnant Sprague-Dawley rats were exposed to either an ad libitum liquid diet containing 35% ethanol-derived calories, an isocalorically matched liquid diet, or a diet consisting of laboratory chow and water. Regional alterations in catecholamine content and turnover in each of the brain areas were observed on postnatal Day 18. A regional variability was demonstrated in the effect of in utero ethanol exposure on catecholamine content and turnover. The most dramatic effect was found in the dopaminergic neurons of the medial basal hypothalamus where in utero ethanol exposed offspring had a significantly reduced DA content and turnover when compared to pups from both isocalorically matched and chow-fed dams. These data indicate that the dopaminergic neurons of this particular brain region are susceptible to alteration by ethanol exposure during development and that this alteration cannot be explained by changes in nutrition alone.

Animals↗