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PubMed2001

Leptin stimulates catecholamine synthesis in a PKC-dependent manner in cultured porcine adrenal medullary chromaffin cells.

We have previously shown that murine recombinant leptin directly stimulates catecholamine synthesis through the long form of the leptin receptor (Ob-Rb) expressed in cultured porcine chromaffin cells. Additionally, we found that leptin activates IP3 production after PLC activation. It is well established that activation of PLC elicits IP3 production as well as an increase in diacylglycerol, a compound that stimulates PKC. Therefore, we investigated the involvement of PKC in leptin-induced catecholamine synthesis. Leptin was found to induce significant increases in PKC activity in a dose-dependent manner (1, 10, and 100 nM); chelation of extracellular Ca(2+) by EDTA abolished this PKC stimulatory activity. We also confirmed by Western blot analysis that leptin (at 100 nM) induced significant increases in Ca(2+)-dependent PKC alpha, -beta(I), and -gamma expression. The activity of the rate-limiting enzyme tyrosine hydroxylase (TH) in the biosynthesis of catecholamine is regulated at the transcriptional and posttranscriptional levels. TH enzyme activity and TH mRNA levels induced by 100 nM leptin were significantly inhibited by the PKC inhibitor Ro 32-0432 as well as by EDTA. In addition, increases in TH protein and intracellular catecholamine content stimulated by leptin were completely inhibited by Ro 32-0432. Leptin markedly activated ERKs and, to a lesser extent, JNK; these stimulatory effects on ERKs and JNK were completely inhibited by Ro 32-0432 as well as EDTA. In contrast, leptin did not activate P38 MAPK. Similar to leptin, PMA activated ERK and JNK. Nicardipine and omega-conotoxin GVIA, each at 1 microM, were effective at inhibiting leptin-induced TH enzyme activity, TH mRNA accumulation, PKC activity, and ERK activity. Leptin increased activating protein-1 DNA-binding activity, and this was diminished by Ro 32-0432 as well as EDTA, similar to the reduction of TH mRNA levels. In addition, using supershift analysis, we documented the involvement of c-Fos and, to a lesser extent, c-Jun in leptin-induced activating protein-1 activity. These results indicate that leptin stimulates Ca(2+)-dependent PKC isoform-dependent catecholamine synthesis in porcine chromaffin cells. Previously, we had shown that leptin stimulated cAMP. The present study also showed that H89 (a PKA inhibitor) moderately, but significantly, inhibited leptin-induced ERK and TH mRNA. Consistent with this finding, leptin is shown here to activate novel PKC epsilon, which is assumed to stimulate Raf, upstream of ERKs, via cAMP, supporting the suggestion that Ca(2+)-independent novel PKC may also play some physiological role in regulating catecholamine synthesis.

Adrenal Medulla↗
PubMed1986

Plasma catecholamines, dietary carbohydrate, and glucose intolerance: a comparison between young and old men.

Catecholamines play an important role in glucose homeostasis. This study was designed to determine whether circulating catecholamine changes in the elderly play a role in the glucose intolerance of aging and whether these changes are related to dietary carbohydrate intake. Plasma catecholamines (epinephrine and norepinephrine) and glucose were measured before and for 2 h after the administration of 100 g oral glucose in both 18 young (age, 18-39 yr) and 20 old (age, 60-82 yr) normal men during ad libitum home diet and after 3-day weight-maintaining, high or low carbohydrate formula diets in the Clinical Research Center. The elderly men had higher plasma norepinephrine levels before and after oral glucose than the young men even when eating matched formula diets. Plasma epinephrine levels were similar and decreased significantly after oral glucose in both groups. There was no relationship between catecholamine levels and degree of glucose tolerance. A high carbohydrate diet improved glucose tolerance in both old and young subjects. However, changes in dietary carbohydrates were not associated with consistent changes in plasma catecholamines. Therefore, we conclude that 1) glucose intolerance of aging cannot be explained by changes in plasma catecholamines, 2) the age-related increase in plasma norepinephrine is unrelated to dietary carbohydrate intake, and 3) there is no effect of age on suppression of plasma epinephrine after oral glucose administration.

Adolescent↗
PubMed2000

Primary structure and function of the catecholamine release inhibitory peptide catestatin (chromogranin A(344-364)): identification of amino acid residues crucial for activity.

The novel chromogranin A fragment catestatin (bovine chromogranin A(344-364); RSMRLSFRARGYGFRGPGLQL) is a potent inhibitor of catecholamine release (IC50, approximately 0.2-0.3 microM) by acting as a nicotinic cholinergic antagonist. To define the minimal active region within catestatin, we tested the potencies of synthetic serial three-residue deletion (amino-terminal, carboxyl-terminal, or bidirectional) fragments to inhibit nicotine-stimulated catecholamine secretion from PC12 pheochromocytoma cells. The results revealed that a completely active core sequence of catestatin was constituted by chromogranin A(344-364). Nicotinic cationic signal transduction was affected by catestatin fragments in a manner similar to that for secretion (confirming the functional importance of the amino-terminus). To identify crucial residues within the active core, we tested serial single amino acid truncations or single residue substitutions by alanine on nicotine-induced catecholamine secretion and desensitization. Nicotinic inhibition by the active catestatin core was diminished by even single amino acid deletions. Selective alanine substitution mutagenesis of the active core revealed important roles for Met346, Leu348, Phe350, Arg351, Arg353, Gly354, Tyr355, Phe357, and Arg358 on catecholamine secretion, whereas crucial roles to inhibit desensitization of catecholamine release were noted for Arg344, Met346, Leu348, Ser349, Phe350, Arg353, Gly354, Tyr355, Gly356, and Arg358. We conclude that a small, 15-amino acid core of catestatin (chromogranin A(344-364)) is sufficient to exert the peptide's typical inhibitory effects on nicotinic cholinergic-stimulated catecholamine secretion, signal transduction, and desensitization. These studies refine the biologically active domains of catestatin and suggest that the pharmacophores for inhibition of nicotinic secretion and desensitization may not be identical.

Amino Acid Sequence↗
PubMed2003

Catecholamine secretion in trout chromaffin cells experiencing nicotinic receptor desensitization is maintained by non-cholinergic neurotransmission.

The goal of the present study was to assess the catecholamine secretory capabilities of rainbow trout Oncorhynchus mykiss chromaffin cells experiencing desensitization of the nicotinic receptor. It was hypothesized that the potential to secrete catecholamines could be maintained under conditions of nicotinic receptor desensitization owing to activation of non-cholinergic release pathways. An in situ model for chromaffin cell nicotinic receptor desensitization was developed by perfusing a posterior cardinal vein preparation with saline containing 10(-5) mol l(-1) nicotine. Under such conditions of desensitization, the chromaffin cells were largely unresponsive to high-frequency (20 Hz) electrical stimulation; the minimal remaining secretory response was abolished by addition of the nicotinic receptor antagonist hexamethonium (10(-3) mol l(-1)). In marked contrast, however, the capacity to secrete catecholamines in response to low-frequency (1 Hz) electrical stimulation was unaffected by nicotinic receptor desensitization or by cholinergic receptor blockade (hexamethonium plus atropine). In preparations experiencing nicotinic receptor desensitization, the stimulatory effect of low-frequency (1 Hz) stimulation on catecholamine secretion was reduced by 43% in the presence of the VPAC receptor antagonist, VIP(6-28). The stimulatory effect of high-frequency (20 Hz) stimulation was unaffected by VIP(6-28). Catecholamine secretion evoked by cod VIP (10(-11) mol kg(-1)) and homologous angiotensin II ([Asn(1), Val(5)] Ang II; 5 x 10(-7) mol kg(-1)) was markedly enhanced (107 and 97%, respectively) in desensitized preparations. However, the secretory response to the muscarinic receptor agonist methylcholine (1 x 10(-3) mol kg(-1)) was unchanged by desensitization. The results of this study demonstrate that exploitation of non-cholinergic mechanisms, including peptidergic pathways activated during low-frequency neuronal stimulation, is a potential strategy whereby catecholamine secretion from trout chromaffin cells can be maintained during periods of nicotinic receptor desensitization.

Animals↗
PubMed1999

Neuronal control of catecholamine secretion from chromaffin cells in the rainbow trout (Oncorhynchus mykiss).

The goal of the present investigation was to assess the relative involvement of nicotinic and muscarinic cholinergic receptors in the neuronal control of catecholamine secretion from the chromaffin tissue of rainbow trout (Oncorhynchus mykiss). This was accomplished by first developing and validating a nerve-stimulating technique able specifically to activate the nerve fibres innervating the chromaffin cells in order to elicit secretion of catecholamines. Using an in situ saline-perfused posterior cardinal vein preparation, it was demonstrated that whole-body field stimulation caused specific voltage-dependent neuronal stimulation of adrenaline and noradrenaline secretion. The contribution of non-specific depolarization was negligible. Several experimental results confirmed the specificity of the field stimulation technique. First, pre-treatment with neostigmine (an anticholinesterase) prolonged and more than doubled the amount of adrenaline secreted in response to electrical stimulation. Second, pre-treatment with the nicotinic receptor antagonist hexamethonium inhibited the electrically evoked secretion of adrenaline and noradrenaline. Third, perfusion with Na+-free saline or removal of the spinal cord abolished secretion of both catecholamines in response to the electrical stimulus. By using the field stimulation technique, this study is the first to demonstrate conclusively a role for muscarinic receptors in catecholamine secretion from trout chromaffin cells. Specifically, muscarinic cholinergic stimulation enhances nicotinic-evoked secretion of catecholamines and, under intense stimulation, may directly cause secretion. The results of the present study suggest the presence of muscarinic receptors on rainbow trout chromaffin cells with a functional role in the cholinergic control of catecholamine secretion.

Animals↗
PubMed1982

Pharmacological studies on Chinese cinnamon. V. Catecholamine releasing effect of cinnamaldehyde in dogs.

Effect of i.v. and i.d. cinnamaldehyde on plasma catecholamine concentration along with intestinal absorption of the drug was studied in anesthetized dogs. Cinnamaldehyde increased plasma catecholamine concentration, the effect produced through i.d. route (50-100 mg/kg) being dose-dependent and more lasting compared with that through i.v. route (20 mg/kg). In the case of 200 mg/kg of i.d. cinnamaldehyde, an exceeding increase in this parameter was obtained during the later period of time course. Intestinal absorption of cinnamaldehyde i.d. administered, which was investigated through measurement of cinnamaldehyde concentration in the portal venous blood and in blood of the postcava, occurred very early and was long-lasting. Increase in plasma catecholamine concentration produced by i.v. cinnamaldehyde disappeared after blood circulation through the adrenal glands was stopped, and was not influenced with pretreatment of hexamethonium plus atropine. Almost all the increased portion of plasma catecholamines by i.v. or i.d. cinnamaldehyde was epinephrine. It was concluded that cinnamaldehyde, entering the circulatory system, reaches the adrenals and releases catecholamines from the organ through a mechanism(s) independent of affecting the cholinergic system. i.v. DMPP which was used as a referential drug also increased plasma catecholamine concentration.

Acrolein↗
PubMed1979

Plasma catecholamines determination using high pressure liquid chromatography and their roles in blood pressure regulation and experimental hypertension in rats.

Plasma catecholamine levels have been used experiemtally and clinically as the indices of the sympathetic nerve activity. We measured plasma catecholamines using high pressure liquid chromatography in rats to assess the significance of plasma catecholamines as an index of the sympathetic nerve activity and its role in hypertension. Pentobarbital anesthesia depressed plasma catecholamine levels, especially plasma adrenaline. Sodium loading for 5 weeks suppressed plasma noradrenaline, while administration of furosemide (1 mg/kg) produced the elevation of plasma noradrenaline. Experimental hypertension, one-kidney and two-kidney types of Goldblatt hypertension and DOCA-salt hypertension, raised plasma noradrenalines both in acute and chronic phases. The infusion of pressor doses of angiotensin II suppressed plasma noradrenaline by the reflex mechanism. Sar1, Ile8-angiotensin II and SQ 14,225 did not suppress plasma cathecholamine elevation due to hemorrhage. L-Hydroxyldopamine produced elevation of plasma catecholamines in experimental nypertension and controls in rats. After adrenal demedullation, plasma noradrenaline was decreased by the administration of 6-hydroxy-dopamine. Acute reduction of circulating blood volume and blood pressure fall produced the elevation of plasma catecholamine, especially plasma adrenaline. In rats, the adrenal medulla plays an important role in the regulation of blood pressure.

Aging↗
PubMed2006

Inhibition by selenium compounds of catecholamine secretion due to inhibition of Ca2+ influx in cultured bovine adrenal chromaffin cells.

Selenium is an essential trace metal element, whereas large doses of selenium exert adverse effects to the human body. We examined the effects of selenium compounds, sodium selenite (Na2SeO3) and sodium selenate (Na2SeO4), on catecholamine secretion from cultured bovine adrenal chromaffin cells. Treatment of chromaffin cells with sodium selenite for 72, 48, and 24 h caused decreases in protein and catecholamine contents, in association with cell damage, at concentrations over 30, 300, and 300 microM, respectively. The cells treated with subtoxic conditions (<100 microM, 48 h) of sodium selenite were used for further experiments. Sodium selenite treatment for 48 h inhibited carbachol (CCh)-induced catecholamine secretion in a concentration-dependent and non-competitive manner, while it did not affect high K+- and veratridine-induced catecholamine secretion. Sodium selenite (100 microM) did not affect CCh- and veratridine-induced 22Na+ influx, while the compound inhibited 45Ca2+ influx induced only by CCh, but not high K+ and veratridine. Sodium selenate even at higher concentrations (1000 microM) did not affect any stimulus-induced catecholamine secretion and 45Ca2+ influx. Thus, sodium selenite may specifically exert adverse effects, such as inhibition of physiological stimulus-induced catecholamine secretion from adrenal chromaffin cells due to inhibition of Ca2+ influx.

Adrenal Medulla↗
PubMed1993

[Extracellular ATP evoked catecholamine release and inositol phosphates formation in cultured porcine adrenal medullary cells].

ATP is ubiquitously present in neural tissues and is released during nerve stimulation. It is known that splanchnic nerve terminals located in adrenal medulla also contain acetylcholine and ATP. These substances may be released concomitantly with nerve stimulation. ATP can exert its effects on neuron-effector junctions by acting directly as a neurotransmitter by increasing or decreasing the release of other neurotransmitters or by modulating their actions. Chern et al. reported that ATP and adenosine inhibited acetylcholine stimulated secretion of catecholamine from isolated bovine adrenal medullary cells. However, Kim et al. showed that extracellular ATP stimulated catecholamine secretion from cultured bovine adrenal medullary cells. Therefore, we investigated the effect of ATP on second messengers levels in cultured porcine adrenal medullary cells as well as catecholamine release from the cells. ATP (500 microM-5mM) evoked catecholamine release significantly (p < 0.05). An unhydrolyzable ATP analogue, ATP gamma S, was several times more potent than ATP in the secretion. ATP-evoked maximal secretion of catecholamine was several times less potent than that evoked by carbachol. Removal of extracellular Ca2+ did not effectively inhibit ATP-induced secretion. 45Ca2+ influx was not observed by the addition of ATP. These results indicated that the catecholamine secretion induced by ATP was independent of extracellular Ca2+. ATP evoked cAMP production slightly at 1mM and did not affect cGMP content. On the other hand, ATP (100 microM-5mM) induced a remarkable increase in inositol trisphosphate, a messenger for mobilization of Ca2+ from intracellular storage sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1985

Catecholamines in the plasma and urine of patients with alcoholic liver damage under resting and exercise conditions.

Heart rate and plasma catecholamines were determined in 16 patients with alcoholic fatty liver and 14 patients with alcoholic cirrhosis of the liver. The measurements were performed at rest and after exercise on the bicycle ergometer, on average 11 days after admission to hospital. In comparison with a control group, the mean heart rate of the patient group was significantly increased at rest and under graduated loading. Significantly increased plasma catecholamine concentrations under resting conditions were observed in both groups of patients, the increase being more pronounced in the cirrhotics (increased with progressive liver damage, significant differences being found between the control group and each of the two groups of patients). During exercise under a load of 50 or 100 watts, the increases in adrenaline, noradrenaline and dopamine concentrations were greatest in patients with alcoholic cirrhosis. With reference to the initial values, however, the increases in concentration were identical in all three groups. In the patients, metabolism of the catecholamines remained unchanged after an average of 11 days abstinence from alcohol; they showed a significantly diminished elimination of vanillylmandelic acid in the urine and, compared with the greatly elevated plasma catecholamine levels, they showed only a moderate increase in the excretion of catecholamines. The results reported here support the assumption that changes in catecholamine metabolism compatible with an increased sympathetic activity are present in chronic alcoholics without advanced liver damage.

Adult↗
PubMed2005

Increased prevalence of catecholamine excess and phaeochromocytomas in a well-defined Dutch population with SDHD-linked head and neck paragangliomas.

OBJECTIVE: The aim of this study was to identify the prevalence of catecholamine excess and phaeochromocytomas in a well-defined population of people with hereditary head and neck paragangliomas. METHODS: We studied in a prospective follow-up protocol all consecutive patients referred to the Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands with documented head and neck paragangliomas and either a positive family history for paragangliomas or a proven SDHD gene mutation. Initial analysis included medical history, physical examination and the measurement of excretion of catecholamines in two 24-h urine collections. In the case of documented catecholamine excess iodinated meta-iodobenzylguanidine (123I-MIBG) scintigraphy and magnetic resonance imaging were done. RESULTS: Between 1988 and 2003, 40 consecutive patients (20 male and 20 female) with documented head and neck paragangliomas were screened. Biochemical screening revealed urinary catecholamine excess in 15 patients (37.5%). In nine of these 15 patients a lesion was found by 123I-MIBG scintigraphy. Exact localization by magnetic resonance imaging revealed phaeochromocytomas in seven of the 15 patients. One of the nine patients had an extra-adrenal paraganglioma. Histopathological examination in a subset of tumors displayed loss of heterozygosity of the wild-type SDHD allele in all cases. CONCLUSIONS: The prevalence of catecholamine excess (37.5%) and phaeochromocytomas (20.0%) is high in patients with familial head and neck paragangliomas. Therefore, patients with hereditary head and neck paragangliomas require lifelong follow up by biochemical testing for catecholamine excess.

Adrenal Gland Neoplasms↗
PubMed1999

Mediation of humoral catecholamine secretion by the renin-angiotensin system in hypotensive rainbow trout (Oncorhynchus mykiss).

The individual contributions of, and potential interactions between, the renin-angiotensin system (RAS) and the humoral adrenergic stress response to blood pressure regulation were examined in rainbow trout. Intravenous injection of the smooth muscle relaxant, papaverine (10 mg/kg), elicited a transient decrease in dorsal aortic blood pressure (PDA) and systemic vascular resistance (RS), and significant increases in plasma angiotensin II (Ang II) and catecholamine concentrations. Blockade of alpha-adrenoceptors before papaverine treatment prevented PDA and RS recovery, had no effect on the increase in plasma catecholamines, and resulted in greater plasma Ang II concentrations. Administration of the angiotensin-converting enzyme inhibitor, lisinopril (10(-4) mol/kg), before papaverine treatment attenuated the increases in the plasma concentrations of Ang II, adrenaline, and noradrenaline by 90, 79, and 40%, respectively and also prevented PDA and RS recovery. By itself, lisinopril treatment caused a gradual and sustained decrease in PDA and RS, and reductions in basal plasma Ang II and adrenaline concentrations. Bolus injection of a catecholamine cocktail (4 nmol/kg noradrenaline plus 40 nmol/kg adrenaline) in the lisinopril+papaverine-treated trout, to supplement their circulating catecholamine concentrations and mimic those observed in fish treated only with papaverine, resulted in a temporary recovery in PDA and RS. These results indicate that the RAS and the acute humoral adrenergic response are both recruited during an acute hypotensive stress, and have important roles in the compensatory response to hypotension in rainbow trout. However, whereas the contribution of the RAS to PDA recovery is largely indirect and relies on an Ang II-mediated secretion of catecholamines, the contribution from the adrenergic system is direct and relies at least in part on plasma catecholamines.

Acute Disease↗
PubMed1980

Catecholamine metabolism in a psychoactive cactus.

The Dona Ana cactus, Coryphantha macromeris (Engelm.) Br. and R. and its runyonii (Br. and R.) L. Benson variety are being promoted as natural and legal psychedelic agents with about one-fifth potency of peyote [Lophophora williamsii (Lem.) Coult.]. Like peyote, Dona Ana produces and accumulates various methylated catecholamine derivatives. Of these phenethylamines, normacromerine (N-methyl-3,4-dimethoxy-beta-hydroxyphenethylamine) is by far the most abundant and has been shown to affect animal behavior in such a way as to suggest psychoactivity. It has been demonstrated that the catecholamines epinephrine and norepinephrine occur naturally in C. macromeris var. runyonii and serve as biosynthetic intermediates in normacromerine biosynthesis. Catecholamine precursors and derivatives have also been shown to be part of the metabolic pathway leading to the formation of normacromerine in Dona Ana. Normacromerine appears to be the end product of catecholamine metabolism since recent studies have revealed that very little of this compound is metabolized once it has been formed by the cactus. Completed research of this type has allowed the comparison of catecholamine metabolism leading to the formation of a mind-altering drug in a cactus plant and the metabolism of catecholamines in humans. These data together with evidence from future research will allow biochemical analogies which may suggest etiologies for certain types of mental illness.

Alkaloids↗
PubMed1988

Some pungent principles of spices cause the adrenal medulla to secrete catecholamine in anesthetized rats.

We recently reported that capsaicin, a pungent principle of hot red pepper, evokes catecholamine secretion from the rat adrenal medulla. In this study, the effects of some pungent principles of spices on adrenal catecholamine secretion were investigated as compared with that of capsaicin. An increase in catecholamine, especially epinephrine, secretion was observed not only on capsaicin infusion but also on piperine (a pungent principle of pepper) and zingerone (ginger) infusion. Even on infusion of the same amount (650 nmol/kg, i.v.), the order of potency as to catecholamine secretion was capsaicin much greater than piperine greater than or equal to zingerone. While, sulfur-containing and volatile pungent principles, allylisothiocyanate (mustard, etc.) and diallyldisulfide (garlic, etc.), did not even cause slight catecholamine secretion. Furthermore, these adrenergic secretagogues were readily transported via the gut into the body. These results indicate that some pungent principles of dietary spices can induce a warming action via adrenal catecholamine secretion.

Adrenal Medulla↗
PubMed1999

Evaluation of a new method for the analysis of free catecholamines in plasma using automated sample trace enrichment with dialysis and HPLC.

BACKGROUND: Analysis of urinary free catecholamines was automated recently, but analysis of plasma samples posed special difficulties. The present study was undertaken to evaluate a new method for the automated analysis of plasma catecholamines. METHODS: The procedure is based on an improved sample handling system that includes dialysis and sample clean-up on a strong cation trace-enrichment cartridge. The catecholamines norepinephrine, epinephrine, and dopamine are then separated by reversed-phase ion-pair chromatography and quantified by electrochemical detection. RESULTS: Use of a 740- microL sample is required to give the catecholamine detection limit of 0.05 nmol/L and analytical imprecision (CV) between 1.1% and 9.3%. The assay can be run unattended, although >12 h of analysis time is not recommended without cooling of the autosampler rack. Comparison (n = 68) of the automated cation-exchange clean-up with the well-established manual alumina procedure gave excellent agreement (mean, 3.78 +/- 2.76 and 3.8 +/- 2.89 nmol/L for norepinephrine and 0.99 +/- 1.72 and 1.08 +/- 1.78 nmol/L for epinephrine). Hemodialysis had no clear effect on plasma norepinephrine. Epinephrine concentrations were similar (0.05 < P < 0.1) in chronic renal failure patients (0.24 +/- 0.3 nmol/L; n = 15) and healthy controls (0.5 +/- 0.24 nmol/L; n = 31). Dopamine was not quantified, being usually <0.2 nmol/L. CONCLUSION: The availability of such a fully automated procedure should encourage the more widespread use of plasma catecholamine estimation, e.g., after dialysis, exercise, or trauma/surgery and in the investigation of catecholamine-secreting tumors, particularly in the anuric patient.

Autoanalysis↗
PubMed1976

[Urinary excretion of the catecholamines adrenaline, noradrenaline and dopamine as well as the derivatives metanephrine and normetanephrine in heart disease patients].

In 20 normal persons and in 57 patients with heart diseases with functional class I-IV (according to the classification of the New York Heart Association) the 24 hour urinary excretion of the catecholamines adrenaline, noradrenaline and dopamine and of the O2-methylated degradation products metanephrine and normetanephrine was determined. The 3 catecholamines and the 2 O-methylated derivatives were measured simultaneously using chromatographic extraction and purification (Bio-Rex 70) and selective flurometric determination. The following results could be obtained: 1. The urinary excretion of noradrenaline increased with increasing severity of the heart disease. 2. In patients with severe congestive heart failure (functional class IV) in addition the adrenaline excretion in addition the adrenaline excretion increased significantly. 3. There was no relationship between the urinary excretion of dopamine and the severity of the heart disease. 4. The ratio of noradrenaline excretion to dopamine excretion increased with increasing severity of the heart disease, indicating an increased activity of dopamine-mu-hydroxylation in patients with congestive heart failure. 5. The excretion of the O-methylated degradation products metanephrine and normetanephrine in normal persons and in patients with heart diseases paralleled the excretion of the corresponding catecholamines adrenaline and noradrenaline. This indicates, that increased excretion of noradrenaline and adrenaline (Class IV) in patients with heart failure was not due to impaired catecholamine-degradation but indead to increased catecholamine-release indicating increased sympatho-adrenergic activity. These results show in addition that also in patients with heart failure O-methylation represents still the main degradation step for the inactivation of the circulating catecholamines. 6. The relationship of toal excretion of 0-methylated derivates to total excretion of adrenaline and noradrenaline, however, decreased with increasing severity of heart disease, indicating a relative impairment of O-methylation under the condition of severe congestive heart failure.

Adult↗
PubMed1975

Catecholamines and drug-behavior interactions.

The effects of several drugs on schedule-controlled operant behavior depend on the baseline rate of responding and on the nature of the environmental conditions that maintain the behavior. For example, the effects of amphetamine and alpha-methylpara-tyrosine (alphaMT) on operant performances depend to a large extent on the rate at which organisms respond under nondrug control conditions. A neurochemical mechanism for these rate-dependent effects has not been established. However, several lines of evidence suggest that catecholamines are functionally important in the maintenance of many types of behavior, including operant behavior. The fact that many drugs which exhibit drug-behavior interactions also produce characteristic effects on the metabolism of central nervous system catecholamines suggests that the performance of operant behavior per se modifies brain catecholamine metabolism and thereby the subsequent drug effect. Experiments measuring the depletion of catecholamines following synthesis inhibition with alphaMT, or changes in the specific activity of norepinephrine after tritium labeling, have shown that operant behavior alters the metabolism of catecholamines. Preliminary evidence is also presented from experiments designed to determine variables associated with the performance-induced changes in catecholamine metabolism. These variables include: rate of responses; rate or density of reinforcement; and response-reinforcer contingencies. The results of these experiments suggest a neurochemical mechanism for the rate-dependent effects of amphetamine and alphaMT. A model is presented that may account for the general phenomenon of drug-behavior interactions in neurochemical terms.

Animals↗
PubMed2002

Immunomodulatory effects of vasoactive catecholamines.

The immunological side effects of catecholamines have recently gained specific attention in the area of sepsis related research, since stimulation of adrenergic and dopaminergic receptors can lead to a modulation of the cytokine network. Catecholamines alter the production of these immune mediators in peripheral blood cells but also in various tissues such as liver, spleen, lung, heart, kidney and the skin. The sympathetic regulation of cytokines is highly dependent on which type of receptor is stimulated. Whereas ligation of the alpha-adrenoreceptor is associated with predominantly immunostimulating effects (i.e. the induction of TNF alpha and IL-1 beta), stimulation of the beta-adrenoreceptor usually has immunosuppressive consequences (i.e. inhibition of TNF alpha and IL-1 beta, induction of IL-10). In case both receptors are stimulated (i.e. by epinephrine) the beta-adrenoreceptor mediated effects usually dominate those induced by alpha-adrenoreceptor stimulation. Moreover, the adrenergic immunostimulation can be differentially regulated depending on which type of cell or tissue is stimulated. This suggests locoregional effects. Dopaminergic immunomodulation is dominated by immunosuppressive effects, such as the induction of IL-6, the inhibition of TNF alpha, the attenuation of the chemoattractant effect of IL-8 and the inhibition of endothelial adhesion. Catecholamines also alter the number and function of neutrophils and lymphocytes. This again depends on which type of receptor is stimulated. Whereas beta-adrenergic stimulation leads to lymphocytosis, alpha-adrenoreceptors mediate lymphocyte homing. Catecholamine induced neutrophilia involves alpha 1-adrenoreceptor ligation. With respect to neutrophil function, epinephrine increases the respiratory burst. Up to now, most of the available data on catecholamine-induced immunomodulation were obtained in experimental settings. The overwhelming, clear results indicate that this system might have important implications for the pathophysiology of immunological diseases such as septic shock, which are accompanied by increased levels of catecholamines.

Animals↗