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Potentiation by apamin of histamine-stimulated catecholamine biosynthesis and tyrosine hydroxylase phosphorylation in cultured bovine adrenal chromaffin cells.

The effects of small-conductance Ca2(+)-activated K+ channel (SK channel) blocker, apamin, on histamine-stimulated catecholamine biosynthesis and tyrosine hydroxylase phosphorylation in cultured bovine adrenal chromaffin cells were investigated. Histamine (10(-10)-10(-6) M) stimulated [14C]catecholamine biosynthesis from [14C]tyrosine (but not from [14C]DOPA). Apamin (10(-6) M) enhanced the histamine-stimulated catecholamine biosynthesis, which was abolished by omission of extracellular Ca2+. Histamine increased the intracellular free Ca2+ concentration ([Ca2+]i), and this increased [Ca2+]i was potentiated by the presence of apamin. The increase in histamine-stimulated catecholamine biosynthesis with apamin was sensitive to the inhibitors of protein kinase C and Ca2+/calmodulin dependent protein kinase. Apamin increased the histamine-induced phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis. These results suggest that in cultured bovine adrenal chromaffin cells the inhibition of SK channel results in potentiation of catecholamine biosynthesis and tyrosine hydroxylase phosphorylation induced by histamine and that these stimulatory effects may result from the activation of protein kinase C and Ca2+/calmodulin-dependent protein kinase through an increase in [Ca2+]i.

Animals↗

Studies of a transplantable rat pheochromocytoma: biochemical characterization and catecholamine secretion.

The biochemistry and secretory characteristics of a transplantable rat pheochromocytoma have been studied. This tumor possesses the enzyme required for the biosynthesis of norepinephrine from tyrosine, and stores large amounts of norepinephrine (33 +/- 3 nmol/mg of protein). The tumor does not have detectable levels of noradrenalin N-methyltransferase, nor does it contain significant amounts of epinephrine. Approximately two-thirds of the catecholamine content, and one-half of the dopamine beta-monoxygenase activity in the tumor can be isolated in a granule fraction by sedimentation. This granule fraction also contains ATP; the molar ratio of catecholamine to ATP in this granule fraction (5.6 +/- 0.9) is similar to that found in granules prepared from normal adrenal glands. Cell suspensions were prepared by mechanical disruption of the tumor. Incubation of these cell suspensions in media containing 56 mM K+, or the divalant cation ionophores, lasolocid or A23187, leads to the release of catecholamine from these cells. The cells do not secrete catecholamine in response to acetycholine. Catecholamine release induced by 56 mM K+ appears to be by exocytosis, since this release is dependent upon extracellular Ca++, and is accompanied by the release of dopamine beta-monooxygenase, but not of lactate dehydrogenase, from the cells. The mechanism by which the ionophores stimulate catecholamine secretion has not been established.

Adenosine Triphosphate↗

Effect of evodiamine on catecholamine secretion from bovine adrenal medulla.

The effect of evodiamine on catecholamine secretion from bovine adrenal medulla was investigated. Evodiamine, a bioactive component isolated from dry unripened fruit of Evodia rutaecarpa Bentham, was found to stimulate the secretion of catecholamine from perfused bovine adrenal medulla at a concentration of 10 microM and its effect persisted for at least 30 min. This stimulatory effect of evodiamine was abolished by omission of Ca2+ from the perfusion fluid. Evodiamine (0.1-10 microM) markedly enhanced the secretion of catecholamine from the adrenal medulla induced by acetylcholine (100 microM or high K+(56 mM). The secretion of catecholamine was promptly enhanced by acetylcholine or high K+, but returned to the control level on treatment for 20 min. However, when evodiamine was added to the perfusion fluid after acetylcholine or high K+ stimulation for 10 min, the secretion of catecholamine again increased greatly. These results indicate that evodiamine not only stimulated the secretion of catecholamine from bovine adrenal medulla but also reversed insensitivity of these cells to acetylcholine or high K+ stimulation.

Adrenal Medulla↗

Catecholamine levels and treatment in chronic heart failure.

Neurohormonal activation is well studied in chronic heart failure, and covers aspects such as abnormalities of plasma catecholamines, particularly since plasma noradrenaline levels have been found to predict impaired prognosis in heart failure patients. This review will concentrate on the information available on circulating levels of adrenaline and noradrenaline. It will discuss how catecholamine levels change during different disease stages from myocardial infarction to severe chronic heart failure. It has been clearly shown that angiotensin converting enzyme (ACE) inhibitors exert particularly beneficial effects in heart failure patients with raised catecholamine levels. Nevertheless, reviewing how a variety of drug and non-drug interventions affect catecholamine levels and patients' survival, it is concluded that the effect on catecholamine levels does not directly correlate with a survival benefit of the respective intervention. Despite their prognostic significance, due to the development of new prognostic markers for patients with chronic heart failure, the overall clinical value of spot catecholamine levels remains limited.

Arousal↗

Evaluation of catecholamine metabolites, mIBG scan, and bone marrow cytology as response markers in stage 4 neuroblastoma.

BACKGROUND: The early biological response has been proved an excellent predictor in acute lymphoblastic leukemia and nephroblastoma. We asked whether catecholamine metabolites, mIBG scan, and bone marrow evaluation might be relevant response markers in disseminated neuroblastoma. PROCEDURE: Three hundred sixty-seven unselected stage 4 neuroblastoma patients treated according the German cooperative trial NB90 were entered into the study. Catecholamine plasma and urine levels were centrally determined by gas chromatography/ mass spectrometry. Bone marrow cytology and mIBG scans were evaluated by local investigators. RESULTS: At diagnosis, mIBG scan was positive in 306 patients (92%), borderline in seven patients (2%), and negative in 19 patients (6%). Bone marrow aspirates were cytologically positive in 292 patients (84%) and negative in 57 patients (16%). Plasma catecholamine levels were elevated in 79% (206 of 260 patients.), urinary levels in 91% (307 of 338 patients). The outcome of patients with normalized mIBG scan after four courses of chemotherapy [5 year EFS (event free survival) 0.22 +/- 0.07] was not superior to the outcome of patients with still abnormal uptake (5 year EFS 0.30 +/- 0.05). The event free survival of patients with still positive bone marrow aspirates after four courses (0.16 +/- 0.06) was inferior to the EFS of patients with negative bone marrow aspirates (0.26 +/- 0.04, P = 0.0054). Urinary catecholamine normalization after four cycles of chemotherapy (5 year EFS 0.35 +/- 0.06 versus 0.26 +/- 0.10) had no influence on outcome, whereas plasma catecholamine normalization after the first (5 year EFS 0.40 +/- 0.09 versus 0.14 +/- 0.07, P= 0.0364) or the fourth cycle (5 year EFS 0.35 +/- 0.06 versus 0.26 +/- 0.10, P = 0.0242) indicated a better outcome. CONCLUSIONS: These data show that serial plasma catecholamine levels and bone marrow aspirates in the course of the disease are useful tools in predicting outcome.

3-Iodobenzylguanidine↗

Occurrence of neurotensinlike immunoreactivity in subpopulations of hypothalamic, mesencephalic, and medullary catecholamine neurons.

By using indirect immunofluorescence histochemistry combined with the elution-restaining technique, the presence of a neurotensinlike peptide in some catecholamine neurons in the rat brain has been demonstrated. At the level of the medulla oblongata neurotensinlike immunoreactivity was observed in most of the small-sized catecholamine (adrenaline) cell bodies in the dorsolateral part of the nucleus of the solitary tract and in some catecholamine (noradrenaline) cells in the medial part. Neurotensin-positive fibers were found throughout the solitary tract nucleus with increasing concentrations in the rostral direction. Very few neurotensin fibers were seen in the vagal dorsal motor nucleus, which contained a dense network of adrenaline fibers. In the ventral mesencephalon, neurotensinlike immunoreactivity was seen mainly in dopamine cell bodies in the ventral tegmental area, including midline structures, with only single examples of coexistence in the substantia nigra. The dopamine cell bodies of both the A9 and A10 cell groups were surrounded by dense to medium-dense networks of neurotensin fibers. In the hypothalamus numerous dopamine neurons in the arcuate nucleus exhibited neurotensinlike immunoreactivity. Neurotensin-positive nerve terminals, partially overlapping catecholamine (mainly dopamine) fibers, were seen in the external layer of the median eminence. The present results demonstrate coexistence of neurotensinlike immunoreactivity and catecholamines in populations of neurons in some of the central catecholamine cell groups and provide a morphological basis for interactions between the peptide and amines.

Animals↗

Plasma catecholamine concentrations are a reliable index of sympathetic vascular tone in patients with cirrhosis.

In patients with cirrhosis, the significance of elevated plasma catecholamine concentrations is unclear. Thus we investigated the relationship between plasma catecholamine concentrations and the hemodynamic effect of pindolol (an index of sympathetic vascular tone) in 10 patients with cirrhosis. Systemic and splanchnic hemodynamics and plasma catecholamine concentrations in the pulmonary artery and the splanchnic veins (hepatic and azygos veins) were studied before and after the oral administration of pindolol (20 mg). In basal conditions patients exhibited a hyperkinetic circulatory syndrome and elevated plasma catecholamine concentrations. Alterations in basal hemodynamics were correlated with plasma epinephrine concentrations but not with norepinephrine. Pindolol administration significantly decreased heart rate and increased right atrial pressure. After pindolol administration, individual hemodynamic changes (cardiac index, systemic vascular resistance, wedged hepatic venous pressure) were significantly correlated with plasma catecholamine concentrations. In conclusion, this study shows that in cirrhotic patients epinephrine may play a role in hemodynamic alterations, and plasma catecholamine concentrations are an index of sympathetic vascular tone.

Epinephrine↗

Effects of inspired air conditions on catecholamine response to exercise in asthma.

The influence of different inspired air conditions on exercise-induced bronchoconstriction (EIB) is well appreciated. However, the mechanism by which this influence is exerted is uncertain. To determine if varied inspired air conditions during exercise could affect the catecholamine response to physical exercise, we had 13 asthmatic and 6 healthy children (aged 10-18 years) undergo two bouts of cycle ergometry tests under different air conditions. One test was done while breathing cold dry (CD) air (temperature, -20.2 degrees C; relative humidity, 0%) and the other while breathing warm humid (WH) air (temperature, 34.3 degrees C; relative humidity, 100%). Forced expiratory volume in 1 second (FEV1) and plasma catecholamine concentrations were recorded before and after exercise. Marked EIB (48 +/- 5% SEM fall in FEV1 from baseline) developed in all asthmatics after the CD exercise, but no EIB was noted after the WH exercise. Normal controls had no EIB under either test conditions. Plasma levels of catecholamines at rest, and the changes that occurred during and after exercise, were comparable within as well as between the groups in both tests. Catecholamines did not rise in asthmatics following development of EIB. These data demonstrate that inspired air conditions do not influence the sympathoadrenal response to exercise, at least as reflected in plasma catecholamine levels. In fact, this response did not differ between asthmatics and normals, irrespective of the development of EIB. These results are consistent with previous reports about impaired catecholamine response of asthmatics to bronchoconstriction.

Adolescent↗

Role of oxidative stress in catecholamine-induced changes in cardiac sarcolemmal Ca2+ transport.

Although an excessive amount of circulating catecholamines is known to induce cardiomyopathy, the mechanisms are poorly understood. This study was undertaken to investigate the role of oxidative stress in catecholamine-induced heart dysfunction. Treatment of rats for 24 h with a high dose (40 mg/kg) of a synthetic catecholamine, isoproterenol, resulted in increased left ventricular end diastolic pressure, depressed rates of pressure development, and pressure decay as well as increased myocardial Ca2+ content. The increased malondialdehyde content, as well as increased formation of conjugated dienes and low glutathione redox ratio were also observed in hearts from animals injected with isoproterenol. Furthermore, depressed cardiac sarcolemmal (SL) ATP-dependent Ca2+ uptake, Ca2+-stimulated ATPase activity, and Na+-dependent Ca2+ accumulation were detected in experimental hearts. All these catecholamine-induced changes in the heart were attenuated by pretreatment of animals with vitamin E, a well-known antioxidant (25 mg/kg/day for 2 days). Depressed cardiac performance, increased myocardial Ca2+ content, and decreased SL ATP-dependent, and Na+-dependent Ca2+ uptake activities were also seen in the isolated rat hearts perfused with adrenochrome, a catecholamine oxidation product (10 to 25 microg/ml). Incubation of SL membrane with different concentrations of adrenochrome also decreased the ATP-dependent and Na+-dependent Ca2+ uptake activities. These findings suggest the occurrence of oxidative stress, which may depress the SL Ca2+ transport and result in the development intracellular Ca2+ overload and heart dysfunction in catecholamine-induced cardiomyopathy.

Animals↗

Inhibition by carbamazepine of various ion channels-mediated catecholamine secretion in cultured bovine adrenal medullary cells.

The effects of carbamazepine (CBZ) on 22Na+ influx, 45Ca2- influx, catecholamine secretion and cyclic GMP production were examined in cultured bovine adrenal medullary cells. 1) CBZ (40-120 mumol/l) inhibited 22Na+ influx evoked by carbachol in a concentration-dependent manner. CBZ inhibited carbachol-evoked 45Ca2- influx and catecholamine secretion at concentrations similar to those which suppressed 22Na+ influx. 2) CBZ (4-120 mumol/l) inhibited veratridine-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion. 3) CBZ (12 or 40-120 mumol/l) suppressed 56 mmol/l K(+)-evoked 45Ca2+ influx and catecholamine secretion, respectively. 4) Combination of CBZ with nitrendipine or omega-agatoxin-IVA produced further inhibition of 56 mmol/l K(+)-evoked 45Ca2+ influx and catecholamine secretion, compared to the effect of CBZ alone, whereas CBZ plus omega-conotoxin-GVIA did not produce any further inhibition. 5) CBZ (40 mumol/l) attenuated the production of cyclic GMP caused by muscarine. These results suggest that CBZ at therapeutic concentrations (16-48 mumol/l; 4-12 micrograms/ml) inhibits catecholamine secretion by interfering with nicotinic acetylcholine receptor-associated ion channels, voltage-dependent Na+ channels and N-type voltage-dependent Ca2+ channels, and may have an antimuscarinic effect in adrenal medullary cells.

Adrenal Medulla↗

Inhibitory effects of propofol on catecholamine secretion and uptake in cultured bovine adrenal medullary cells.

In the central and peripheral noradrenergic neurons, the balance between noradrenaline release and reuptake determines the level of noradrenaline at the synaptic cleft or the nerve ending. In the present study, we examined the effects of propofol, an intravenous general anaesthetic, on catecholamine secretion and noradrenaline uptake in cultured bovine adrenal medullary cells and on the serum noradrenaline and blood pressure in rats. In cultured adrenal medullary cells, propofol (10-50 mumol/l) concentration-dependently inhibited catecholamine secretion stimulated by carbachol. Propofol suppressed carbachol-evoked 22Na+ influx as well as 45Ca2+ influx at concentrations similar to those which suppressed the catecholamine secretion. Propofol (10-50 mumol/l) also inhibited veratridine-evoked 22Na+ influx, 45Ca2+ influx and catecholamine secretion, whereas it had little effect on the 45Ca2+ influx and catecholamine secretion induced by 56 mmol/l K+. Cultured adrenal medullary cells show [3H] noradrenaline uptake which is sensitive to imipramine. Propofol (10-50 mumol/l) significantly inhibited the imipramine-sensitive uptake of [3H] noradrenaline. In rats, intravenous administration of propofol (2.5 mg/kg) lowered serum noradrenaline and arterial blood pressure. From these findings, in spite of inhibiting noradrenaline uptake, propofol at anaesthetic concentrations (10-30 mumol/l) seems to reduce catecholamine secretion by interfering with Na+ influx through voltage-dependent Na+ channels as well as nicotinic acetylcholine receptor-associated ion channels in the adrenal medulla and, probably, in the sympathetic nervous system. This may explain the propofol-induced hypotension during anaesthesia.

Adrenal Medulla↗

Differential requirements for Ca2+ concentrations for catecholamine release and biosynthesis in isolated bovine adrenal chromaffin cells.

Differential effects of [Ca2+] on catecholamine release and biosynthesis in isolated bovine adrenal chromaffin cells were investigated. Carbamylcholine, an agonist of the nicotinic and muscarinic acetylcholine receptor, or Na+ deprivation in the incubation medium, stimulated catecholamine release and biosynthesis in these cells. The concentrations of extracellular [Ca2+] which stimulate catecholamine biosynthesis were less than those which stimulate catecholamine release. An increase in intracellular levels of free Ca2+ ([Ca2+]i) induced by Na+ deprivation was dependent on extracellular [Ca2+]. These results indicate that, in bovine adrenal chromaffin cells, catecholamine biosynthesis is regulated by lower levels of [Ca2+]i than is catecholamine release.

Adrenal Medulla↗

Cholinoceptor-mediated control of catecholamine release from chromaffin cells in the American eel, Anguilla rostrata.

The cholinergic agonist-induced secretion of catecholamines from chromaffin cells in the American eel, Anguilla rostrata, was assessed using a saline-perfused posterior cardinal vein preparation. Direct membrane depolarization with 60 mmol.l-1 K+ caused a significant release of catecholamines (adrenaline+noradrenaline) into the perfusate which was unaffected by pre-treatment with the ganglion blocker, hexamethonium (final concentration = 10(-3) mol.l-1). The nicotinic receptor agonist, 1,1-dimethyl-4-phenyl-piperazinium iodide, evoked catecholamine release in response to several doses exceeding 10(-7) mol; at 10(-5) mol the response was abolished by pre-treatment with the ganglion blocker, hexamethonium (final concentration = 10(-3) mol.l-1). The muscarinic receptor agonist, pilocarpine, did not elicit catecholamine release in response to any of the doses administered (10(-8)-10(-4) mol). A single injection of the mixed nicotinic/muscarinic cholinoceptor agonist, carbachol (10(-5) mol), caused the release of catecholamines which was abolished by pre-treatment with hexamethonium but which was unaffected by pre-treatment with the muscarinic receptor antagonist atropine (final concentration = 10(-5) mol.l-1). The results of this study indicate that the process of cholinergic agonist-induced catecholamine secretion from the chromaffin cells in the American eel is mediated exclusively by activation of nicotinic receptors with no involvement of the muscarinic receptor.

Animals↗

Catecholamines modulate growth and differentiation of human preosteoclastic cells.

Using a clonal cell line of human osteoclast precursors (FLG 29.1 cells), that after treatment with 12-O-tetradecanoyl phorbol 13-acetate (TPA) show many functional characteristics of osteoclasts, we demonstrated that catecholamines act as inducers of osteoclast maturation in vitro and as stimulators of osteoclast activity via the binding to beta 2 adrenergic receptors. Scatchard analysis of 125I-labelled iodocyanopindolol to untreated (undifferentiated) or TPA-treated (differentiated) FLG 29.1 cells revealed the presence of a single high-affinity site with a Kd value around 24 pM and 8 pM respectively and with superimposable binding capacity (1.18 fmol/mg protein). Catecholamines increased in a dose-dependent fashion the intracellular cyclic AMP (cAMP) accumulation in both undifferentiated and TPA-treated FLG 29.1 cells. Pretreatment of untreated and TPA-treated FLG 29.1 cells with propranolol inhibited the catecholamine effect on cAMP accumulation, while pretreatment with clonidine had no effect. Catecholamines also reduced cell proliferation, increased tartrate-resistant acid phosphatase (TRAcP) activity, interleukin 6 (IL-6) production, multi-nuclearity and response to salmon calcitonin (sCT) in undifferentiated FLG 29.1 cells. In differentiated FLG 29.1 cells only IL-6 release was induced by catecholamine treatment. These findings support a potential role for catecholamines in modulating osteoclast differentiation and mature osteoclast activity.

Adrenergic Antagonists↗

Tyrosine loading in patients with hepatic cirrhosis: lack of effect on plasma catecholamines.

Plasma norepinephrine concentrations are often elevated in patients with hepatic cirrhosis in relation to the stage of disease and possibly in response to a decrease in "effective" arterial blood volume. Since tyrosine, the precursor for catecholamines, is said to influence the rate of catecholamine biosynthesis within the central nervous system and peripheral sympathetic structures, we tested whether basal hypertyrosinemia and increased plasma tyrosine levels after oral loading with l-tyrosine are associated with elevated plasma catecholamine concentrations. Baseline norepinephrine (NE) and epinephrine (E) were significantly higher in 17 patients with decompensated cirrhosis, as compared with 11 healthy controls (NE: 809 +/- 108 pg/ml vs 295 +/- 16 pg/ml; E: 69 +/- 9 pg/ml vs 36 +/- 8 pg/ml). No significant correlation between the basal plasma tyrosine and norepinephrine level could be demonstrated in patients with cirrhosis (r = 0.04). Oral tyrosine loading (100 mg/kg b.w.) administered in six equal doses did not change the level of catecholamines, whereas plasma tyrosine increased two- to three-fold. Even a large single dose (14 g l-tyrosine) failed to alter plasma catecholamines in six cirrhotic patients with marked ascites. We therefore conclude that the enhanced availability of tyrosine in cirrhotics does not influence catecholamine biosynthesis in peripheral sympathetic neurons.

Blood Pressure↗

Correlates of venous catecholamine concentrations in patients with type 1 diabetes during a cold pressor test.

In some patients with type 1 diabetes, various physiologic reactions during a cold pressor test (CPT) are impaired. Whether this is caused by diabetic autonomic neuropathy, disturbed secretion of catecholamines, or disturbed blood glucose control is unknown. The authors, therefore, performed CPTs in patients with type 1 diabetes and in control subjects. They measured blood glucose concentrations, insulin concentrations, cardiac autonomic reflexes, and (before and after the CPT) venous catecholamine concentrations and analyzed correlations between these variables. Twenty-two patients with type 1 diabetes (17 men, 5 women; mean age +/- SD, 26.6 +/- 6.5 y; diabetes duration, 7.6 +/- 0.7 y; glycosylated hemoglobin concentration, 7.7 +/- 2.4%) and 35 control subjects with comparable age and gender distributions were studied. Venous catecholamines were measured before and at the end of a 5-minute CPT. In patients with diabetes, only noradrenaline concentrations increased during the CPT, whereas adrenaline concentrations that were already increased at rest did not change. Adrenaline concentrations correlated inversely with insulin concentrations. In control subjects, both adrenaline and noradrenaline increased significantly during the CPT. In both groups, the magnitude of the individual change in catecholamine concentrations was inversely correlated with the respective resting concentration. Changes in catecholamines, cardiovascular reflex tests, and blood glucose concentrations did not correlate with blood pressure changes. The authors conclude that, in patients with diabetes, resting adrenaline concentrations are related to insulin concentrations. Contrary to control subjects, in patients with diabetes, only noradrenaline increased during CPTs. In both groups, changes in catecholamine concentrations after the CPT were inversely related to the respective resting concentrations.

Adult↗

Fetal catecholamine release with preterm delivery.

Neurosympathetic system activity at birth was studied by measuring umbilical arterial plasma catecholamine concentrations in 36 preterm fetuses. Umbilical arterial catecholamine concentrations were correlated with blood gas status, mode of delivery, fetal sex, and fetal heart rate patterns. Significant correlations were observed for plasma norepinephrine and epinephrine versus fetal pH and PO2 and for plasma dopamine versus pH but not PO2. These catecholamine relationships to acidosis and hypoxia were similar to those of our previously published data for term fetuses. Norepinephrine and dopamine concentrations were similar in both preterm and term fetuses; however, epinephrine levels were significantly greater in preterm fetuses than in term fetuses. Increased concentrations of norepinephrine, epinephrine, and dopamine were observed in association with abnormal fetal heart rate patterns. There was no significant effect of fetal sex on the catecholamine secretory response. Similar cord catecholamine concentrations were observed following vaginal and cesarean section delivery, the latter with and without labor. These results indicate that the preterm fetus, like the term fetus, responds to stress at delivery with a graded catecholamine release. The observation of greater epinephrine concentrations in preterm fetuses than in term fetuses may reflect increased secretion or decreased clearance of epinephrine.

Dopamine↗

Rat brain cells in primary culture: visualization and measurement of catecholamines.

Catecholamines have been visualized and quantified in primary cultures of whole rat brain. Twenty-one-day old cultures treated with glyoxylic acid and viewed under a fluorescence microscope revealed neurons stained specifically with blue-green catecholamine fluorescence. Brightly stained multipolar cell bodies were seen, along with stained neurites and varicosities, and there was no staining associated with the non-neuronal portion of the culture. Twenty-one-day-old non-neuron-enriched cultures contained 10-20 times less norepinephrine and dopamine than cytosine arabinoside-treated neuron-enriched cultures. The latter cultures contained 10-12 times more norepinephrine than 1-day-old rat brains, demonstrating maturation and differentiation of the cultured neurons. Norepinephrine levels of neuron-enriched cultures were, however, 3 times less than those in 21-day-old rat brains. The cultured neurons had the ability to synthesize catecholamines since levels were decreased with alpha-methyl-p-tryosine. On the other hand, the growth medium contained significant amounts of norepinephrine, but did not have the ability to synthesize catecholamines. It may be concluded that the cellular catecholamines are not derived from the medium in any great amounts. This study provides the basis of a system in which to examine catecholaminergic neurotransmission and peptide catecholamine interactions at the cellular level under semi-defined conditions.

Animals↗