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

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

Role of endogenous PACAP in catecholamine secretion from the rat adrenal gland

We elucidated the contribution of endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) to neurally evoked catecholamine secretion from the isolated perfused rat adrenal gland. Infusion of PACAP (100 nM) increased adrenal epinephrine and norepinephrine output. The PACAP-induced catecholamine output responses were inhibited by the PACAP type I receptor antagonist PACAP- (6-38) (30-3,000 nM) but were resistant to the PACAP type II receptor antagonist [Lys1,Pro2,5,Ara3,4,Tyr6]-vasoactive intestinal peptide (LPAT-VIP; 30-3,000 nM). Transmural electrical stimulation (ES; 1-10 Hz) or infusion of ACh (6-200 nM) increased adrenal epinephrine and norepinephrine output. PACAP-(6-38) (3,000 nM), but not LPAT-VIP, also inhibited the ES-induced catecholamine output responses. However, PACAP-(6-38) did not affect the ACh-induced catecholamine output responses. PACAP at low concentrations (0.3-3 nM), which had no influence on catecholamine output, enhanced the ACh-induced catecholamine output responses, but not the ES-induced catecholamine output responses. These results suggest that PACAP is released from the nerve endings to facilitate the neurally evoked catecholamine secretion through PACAP type I receptors in the rat adrenal gland.     

心肌酶谱、动态心电图及冠状动脉CT血管造影诊断嗜铬细胞瘤儿茶酚胺性心脏损害价值研究

摘要 目的：探讨心肌酶谱、动态心电图及冠状动脉CT血管造影诊断嗜铬细胞瘤儿茶酚胺性心脏损害的临床价值。方法：收集2013年1月-2020年4月在我院诊断为嗜铬细胞瘤患者114例,其中嗜铬细胞瘤儿茶酚胺性心脏损害的患者27例。所有患者均完善术前常规检查（血常规、胸片、动态心电图）、心肌酶谱、心脏超声、冠状动脉CTA等临床资料,并收集患者一般临床资料,如血压、临床症状等。结果：114例嗜铬细胞瘤患者中,27例患者存在嗜铬细胞瘤儿茶酚胺性心脏损害。嗜铬细胞瘤儿茶酚胺性心脏损害患者一般临床资料与嗜铬细胞瘤无儿茶酚胺性心脏损害的患者差异无统计学意义（P＞0.05）。嗜铬细胞瘤儿茶酚胺性心脏损害以高血压为主要表现,临床症状表现多样,可伴有头痛、心悸、多汗三联征表现。114例患者中,26例患者出现心肌酶谱升高,36例患者存在不同程度的心电图异常、24例患者冠状动脉CTA异常,嗜铬细胞瘤儿茶酚胺性心脏损害患者在心肌酶谱、动态心电图及冠状动脉CTA异常例数与嗜铬细胞瘤无儿茶酚胺性心脏损害患者中差异均有统计学意义（P＜0.05）。114例患者中心肌酶谱或心电图或冠状动脉CTA异常的患者总共56例,其中嗜铬细胞瘤儿茶酚胺性心脏损害患者23例,嗜铬细胞瘤无儿茶酚胺性心脏损害患者有33例,差异有统计学意义（P＜0.05）。嗜铬细胞瘤儿茶酚胺性心脏损害患者中,心律失常最为常见。结论：嗜铬细胞瘤儿茶酚胺性心脏损害患者心肌酶谱、动态心电图及冠状动脉CTA均可存在异常表现,但特异性、敏感性不高,三者同时综合分析可以提高临床诊断。     

Synapsin II negatively regulates catecholamine release

We have assessed the role of synapsins in catecholamine release by comparing the properties of exocytosis in adrenal chromaffin cells from wild-type and synapsin triple knock-out (TKO) mice. Brief depolarizations led to a greater amount of catecholamine release in chromaffin cells from TKO mice in comparison to chromaffin cells from wild-type mice. This increase in catecholamine release was due to an increased number of exocytotic events, while the properties of individual quanta of released catecholamine were unchanged. Barium ions produced similar amounts of catecholamine release from TKO and wild-type chromaffin cells, suggesting that the reserve pool of chromaffin granules is unchanged following loss of synapsins. Because expression of synapsin IIa in TKO chromaffin cells rescued the defect in depolarization-induced exocytosis, the TKO phenotype apparently results from loss of synapsin IIa. We conclude that synapsin IIa serves as a negative regulator of catecholamine release and that this protein influences exocytosis from a readily releasable pool of chromaffin granules. Further, because these defects in catecholamine release are different from those observed for glutamate and GABA release in TKO mice, we conclude that the functions of synapsins differ for vesicles containing different types of neurotransmitters.     

Substance P Protects Against Desensitization of the Nicotinic Response in Isolated Adrenal Chromaffin Cells

Substance P, a peptide endogenous to the splanchnic nerve, is known to inhibit the acetylcholine-and nicotine-induced release of catecholamines from isolated adrenal chromaffin cells. In the present study the effect of substance P on desensitization of catecholamine release from these cells was examined. Substance P (10(-5) M) completely protected against desensitization of catecholamine release produced by acetylcholine at 37 degrees C or 23 degrees C and by nicotine at 23 degrees C; substance P also afforded appreciable protection against nicotine-induced desensitization at 37 degrees C. The peptide had no effect on K+-induced desensitization of catecholamine release. Like substance P, d-tubocurarine also prevented nicotinic desensitization. Substance P prevented both of two components of nicotinic desensitization, i.e. the Ca2+-dependent component and the Ca2+-independent, depletion-independent component of desensitization. Substance P had little effect on subsequent catecholamine uptake, indicating that substance P's protection against desensitization is a result of facilitation of catecholamine release rather than inhibition of catecholamine reuptake. Nicotine-induced catecholamine release and nicotinic desensitization of catecholamine release were Na+-independent, although substance P's inhibition of nicotine-induced catecholamine release was reduced by extracellular Na+. These in vitro studies suggest a similar role for substance P in vivo: substance P's protection against nicotinic desensitization may ensure a maintained output of adrenal catecholamines during stress, when the splanchnic nerve releases large amounts of acetylcholine.     

Effect of beta-endorphin on catecholamine levels in the rat hypothalamus and cerebral cortex

The present paper deals with the effect of beta-endorphin on catecholamine content in the hypothalamus and cerebral cortex of male rats. beta-endorphin was found to decrease catecholamine content in the rat brain, with the degree of reduction depending on the brain topography and the time following the peptide administration. 5 min later no changes in catecholamine content were observed either in the hypothalamus or in the cerebral cortex. 20 min later beta-endorphin induced a statistically significant fall of catecholamine concentration in the hypothalamus. A tendency towards its decrease was also observed in the cerebral cortex. 60 min later beta-endorphin produced an insignificant decrease in catecholamine level in both brain areas under study. It may be therefore suggested that beta-endorphin-induced decrease of catecholamine content in the hypothalamus and cerebral cortex represents one of the mechanisms underlying beta-endorphin stimulating action on a number of trophic functions of the hypophysis.     

Tetrapeptides on N- and C-Terminal Regions of Mastoparan Inhibit Catecholamine Release from Chromaffin Cells by Blocking Nicotinic Acetylcholine Receptor

Mastoparan (MP), a tetradecapeptide in wasp venom, has been reported to evoke catecholamine release, but also reported to inhibit secretory response upon nicotinic stimulation in adrenal chromaffin cells. To elucidate the inhibitory mechanism of MP, we examined the effect of two MP fragments (INLK-NH2 and KKIL-NH2) on catecholamine release in bovine adrenal chromaffin cells. These MP fragments inhibited catecholamine release induced by nicotinic stimulation in a noncompetitive manner. These fragments did not affect catecholamine release evoked by high [K+] or by other secretagogues, neither caused catecholamine release by themselves. Replacement by hydrophobic and basic amino acids of the MP fragments enhanced the inhibitory effects on ACh-evoked catecholamine release. Among 23 analogs of the MP fragments, (Nle)3-R-NH2 showed the most potent inhibition with IC50 = 541 microM. These results suggested that the MP fragments selectively inhibit the secretory response to nicotinic stimulation by attacking nAChR on the site(s) made up of hydrophobic and acidic amino acids but other than ACh-binding sites. This mechanism may explain the inhibitory action of MP on nicotine-evoked catecholamine release.     

Role of Catecholamines in the Reproduction of Romanomermis culicivorax

The relative concentrations of catecholamine in the nervous system of the entomophilic nematode Romanomermis culicivorax were measured under different experimental conditions by a glyoxylic acid-induced fluorescence procedure. A greater concentration of catecholamine was recorded in the nervous system of adult males and females than in postparasitic juveniles. A higher concentration of catecholamine occurred in adults maintained in physical contact with the opposite sex than in those maintained in isolation. Adult males maintained with females in the same aqueous medium but physically separated by a barrier displayed a greater concentration of catecholamine in their nervous systems than did males maintained in isolation, but the catecholamine fluorescence intensity of such males was less than in males allowed physical contact with females. In adult males, the fluorescence intensity of catecholamine declined progressively during and after copulation. In adult females, the intensity of catecholamine remained constant before, during, and after copulation. Catecholamine(s) may play a role in regulating copulatory behavior, egg production, or oviposition.     

Microfluorimetric quantitation of catecholamine fluorescence in rat median eminence. II. Turnover changes in hormonal states.

Catecholamine nerve terminals in the rat median eminence have been studied using the fluorescence histochemical technique of Falck and Hillarp in combination with quantitative microfluorimetry. The catecholamine fluorescence intensities recorded from various parts of the median eminence were all found to be within the linear part of the dopamine or noradrenaline concentration-fluorescence relationship as studied in an agar-albumin model system. The catecholamine fluorescence was also found to disappear with time in an exponential manner following tyrosine hydroxylase inhibition produced by alpha-methyl-p-tyrosine methylester (H44/68). Similar results were obtained when measuring the dopamine decline by mass fragmentography in the median eminence after H44/68 treatment. These results and analysis of fluorescence frequency histograms strongly indicate that the catecholamine fluorescence values recorded are proportional to the catecholamine concentration. It is concluded that the microfluorimetric technique used is a reliable method for catecholamine quantitation in discrete nerve terminal areas of the median eminence. The main advantages of the technique are that a high sensitivity and quantitative data on the transmitter content can be obtained in strict relation to the neuroanatomy. Measurement of the catecholamine fluorescence disappearance after H44/68 was used to evaluate catecholamine turnover during various endocrine states. The results showed that two dopamine systems with different transmitter turnover may be distinguished. Tuberinfundibular dopamine neurons projecting to the lateral palisade zone were thus shown to have a slower turnover than those projecting medially to the capillary loops. No definite changes in catecholamine turnover were observed after adrenalectomy and castration in the male, although there was a tendency toward increased noradrenaline turnover in both states. During pregnancy an increase in noradrenaline as well as dopamine turnover was noted. The present results therefore give further evidence for the view that catecholamine nerve terminals in the median eminence may participate in the regulation of gonadotrophin secretion.     

Further studies on the relationship between tyrosine supply and catecholamine production in cultured adrenal chromaffin cells.

To elucidate a possible role of tyrosine supply as a factor modulating catecholamine biosynthesis in the adrenergic cell, the transport of [14C]tyrosine into cultured bovine adrenal chromaffin cells was first examined, and the relationship between [14C]tyrosine transport and [14C]catecholamine formation was then investigated. Under the conditions which were routinely employed to determine the rate of catecholamine biosynthesis, tyrosine was taken up into the cells in a manner independent of extracellular Na+ and Ca2+, and this uptake was also insensitive to ouabain and various metabolic inhibitors. The stimulation of these cells with high K+ and other secretagogues caused no significant alteration in the uptake. While, tyrosine transport was markedly inhibited by tyrosine analogues and other L-aromatic amino acids, and this inhibition was accompanied by the reduction of [14C]catecholamine formation. In contrast, tyrosine transport was markedly enhanced by flavone, and this enhancement was also accompanied by the augmentation of catecholamine production under the same experimental conditions. These results seem to indicate that the transport of tyrosine into the cells may be closely related to catecholamine formation within the cells, thus providing an evidence for a possible role of tyrosine supply as one of the factors affecting catecholamine production in the adrenal chromaffin cell.     

Studies on the Effect of Insulin-Like Growth Factor-I on Catecholamine Secretion from Chromaffin Cells

Chromaffin cells cultured in serum-free medium secreted a smaller percentage of their catecholamine stores in response to stimulation by high K+ (55 mM) than did cells cultured in serum-containing medium. Addition of insulin-like growth factor-I (IGF-I) to serum-free medium restored high K(+)-stimulated catecholamine secretion to the levels seen in serum-treated cultures. In contrast, addition of IGF-I to serum-containing medium had little effect on catecholamine secretion. These results suggest that serum contains IGF-I or another factor that maintains the secretory responsiveness of chromaffin cells. IGF-I not only enhanced high K(+)-stimulated catecholamine secretion, but also augmented secretion elicited by the nicotinic agonist dimethyl-phenylpiperazinium, the dihydropyridine agonist Bay K 8644, and Ba2+. IGF-I did not affect the dependence of catecholamine secretion on extracellular Ca2+ concentration nor did it affect the time course of secretion. Experiments using 45Ca2+ demonstrated that IGF-I treatment enhanced Ca2+ uptake into the cells. When cells were permeabilized by treatment with digitonin, Ca2(+)-dependent catecholamine secretion was slightly, but consistently, greater from IGF-I-treated cells than from untreated cells. Our results suggest that IGF-I may enhance catecholamine secretion partly by increasing Ca2+ entry into the cells and partly by affecting a step distal to Ca2+ entry.     

Catecholamine secretion by hamster adrenal cells.

Abstract— Suspensions of isolated adrenal cells were prepared by digesting hamster adrenal glands with collagenase, and the secretion of catecholamine from these cells was studied. Acetylcholine (ACh) produces a dose-dependent increase in catecholamine secretion; half-maximal secretion is produced by 3 μm -ACh, and maximal secretion by 100 μm -ACh. The cholinergic receptor in these cells appears to be nicotinic, since catecholamine secretion is stimulated by the nicotinic agonists nicotine and dimeth-ylphenylpiperaziniurn, but not by the muscarinic agonists pilocarpine or oxotremorine. ACh-induced catecholamine secretion is inhibited by hexamethonium, tubocurarine, and atropine, but is not inhibited by α-bungarotoxin. ACh-induced catecholamine secretion is dependent upon the presence of extracellular Ca²⁺, and appears to occur by exocytosis, since the release of catecholamine is accompanied by the release of dopamine β-monooxygenase, but not of lactate dehydrogenase. These biochemical studies complement the morphological evidence for exocytosis in hamster adrenal glands, and indicate that catecholamine secretion from hamster chromaffin cells is similar to that from chromaffin cells of other species.     

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.     

Modulation of catecholamine release by endogenous adenosine in the rat adrenal medulla

Adenosine was shown to inhibit norepinephrine (NE) release from sympathetic nerve endings. The purpose of this study was to examine whether endogenous adenosine restrains NE and epinephrine release from the adrenal medulla. The effects of an adenosine receptor antagonist, 1,3-dipropyl-8-(p-sulfophenyl) xanthine (DPSPX), on epinephrine and NE release induced by intravenous administration of insulin in conscious rats were examined. Plasma catecholamines were measured by HPLC with an electrochemical detector. DPSPX significantly increased plasma catecholamine in both control rats and rats treated with insulin. The effect of DPSPX on plasma catecholamine was significantly greater in rats treated with insulin. Additional experiments were performed in adrenalectomized rats to investigate the contribution of the adrenal medulla to the effect of DPSPX on plasma catecholamine. The effect of DPSPX and insulin on epinephrine in adrenalectomized rats was significantly reduced compared with that of the controls. Finally, we tested whether endogenous adenosine restrains catecholamine secretion partially through inhibiting the renin-angiotensin system. The effect of DPSPX on plasma catecholamine in rats pretreated with captopril (an angiotensin-converting enzyme inhibitor) was reduced. These results demonstrate that under basal physiological conditions, endogenous adenosine tonically inhibits catecholamine secretion from the adrenal medulla, and this effect is augmented when the sympathetic system is stimulated. The effect of endogenous adenosine on catecholamine secretion from the adrenal medulla is achieved partially through the inhibitory effect of adenosine on the renin-angiotensin system.     

大鼠肾上腺髓质儿茶酚胺分泌的在体伏安法测定

应用碳纤微电极直接测定大鼠肾上腺髓质中儿茶酚胺浓度的在体伏安法。首次报道了大鼠肾上腺髓质中儿茶酚胺的基础浓度为０．１－０．５μｍｏｌ／Ｌ,缺血时髓质中儿茶酚胺的浓度显著增加,严重缺血时可达到５－３０μｍｏｌ／Ｌ。肾上腺髓质能自发分泌儿茶酚胺,缺血时自发分泌儿茶酚胺的幅度和频率都大大增加,提示缺血对大鼠是一种强烈的应激,测定结果还表明,乙酰胆碱能剂量依赖性地刺激肾上腺髓质嗜铬细胞分泌儿茶酚胺。     

Catecholamine content of chromaffin granule ‘ghosts’ isolated from bovine adrenal glands

Studies on the mechanism of catecholamine transport into chromaffin granules is complicated by the release of endogenous catecholamines. To overcome this problem chromaffin granule ghosts have been prepared by many investigators by osmotic lysis of the granules which results in a loss of over 90% of the endogenous catecholamine. However, in the studies reported here, the resulting ghosts still contained 36 ± 3.9 nmol epinephrine/mg of protein if they were lysed by passage through a Sephadex G-50 column preequilibrated with hypoosmtic media. This residual catecholamine was foun the slowly diffuse out of the ghosts in a temperature-dependent process at a rate sufficient to interfere with kinetic analysis of catecholamine transport. Attempts to remove the endogenous catecholamine from the ghosts indicated that most of it could not be removed by further osmotic shock or freeze-thaw treatments, but that over 85% of it was released from the granules by incubating them at 30°C for 90 min or by dialysis with a 35 and 86% loss of rate of catecholamine transport into the ghosts, respectively. If the endogenous catecholamine was removed from chromaffin granule ghosts by preincubating them for 90 min at 30°C, these resulting ghosts transported catecholamine with a linear Lineweaver-Burk plot indicating a K_m of 12±2 μM. In addition, the resulting ghosts did not leak catecholamines over a 10 min period at 30°C, and the transport of catecholamines was blocked by reserpine and enhanced with increasing pH from 6.0 to 8.5.     

Effect of the rate of blood loss on the plasma catecholamine response

In the present experiments the influence on the sympatho-adrenal system of the rate of haemorrhage-induced blood pressure fall in dogs was studied by measuring the plasma catecholamine response. Bleeding to a mean arterial pressure of 5.3 kPa in either 10 or 40 minutes caused an identical increase in the plasma catecholamine level. Similarly, there was no difference in bleeding volumes between the two groups. Within these limits the magnitude of the early catecholamine response was independent of the rate of the haemorrhage-induced decrease of blood pressure. The magnitude of the sympatho-adrenal response depended on the amount of lost blood. Bleeding for 80 minutes to the same pressure resulted in a considerably larger loss of blood and higher plasma catecholamine levels. No relationship was, however, found between the extent of the catecholamine response and the amount of the bleeding volume, probably due to some interaction with other control mechanisms.     

Catecholamine secretion by isolated adrenal cells.

Isolated adrenal cells were prepared by collagenase digestion of guinea pig adrenal glands. Acetylcholine stimulates the secretion of catecholamines by these isolated adrenal cells. Acetylcholine-stimulated catecholamine secretion is inhibited by cholinergic blocking agents (atropine and hexamethonium) and by local anaesthetics (tetracaine), and is dependent upon the concentration of Ca2+ in the incubation medium. In the presence of Ca2+, catecholamine secretion is also stimulated by two divalent cation ionophores, A23187 and X-537A. Cyclic nucleotides and 5'-nucleotides cause a small, non-specific stimulation of catecholamine secretion. These results indicate that isolated adrenal cells are a useful system in which to study catecholamine secretion, and support the hypothesis that increased Ca2+ entry into chromaffin cells is a sufficient stimulus for catecholamine secretion.     

Bcl‐2‐associated athanogene 5 overexpression attenuates catecholamine‐induced vascular endothelial cell apoptosis

Bcl‐2 associated athanogene 5 (Bag5) is a novel endoplasmic reticulum (ER) regulator. However, its role in catecholamine‐induced endothelial cells damage has not been fully understood. In our study, catecholamine was used to mimic hypertension‐related endothelial cell damage. Then, western blots, enzyme‐linked immunosorbent assay, immunofluorescence, quantitative polymerase chain reaction and pathway analysis were conducted to analyze the role of Bag5 in endothelial cell damage in response to catecholamine. Our results indicated that the endothelial cell viability was impaired by catecholamine. Interestingly, Bag5 overexpression significantly reversed endothelial cell viability. Mechanistically, Bag5 overexpression inhibited ER stress, attenuated oxidative stress and repressed inflammation in catecholamine‐treated endothelial cells. These beneficial effects finally contributed to endothelial cell survival under catecholamine treatment. Pathway analysis demonstrated that Bag5 was under the control of the mitogen‐activated protein kinase (MAPK)–extracellular‐signal‐regulated kinase (ERK) signaling pathway. Reactivation of the MAPK–ERK pathway could upregulate Bag5 expression and thus promote endothelial cell survival through inhibiting oxidative stress, ER stress, and inflammation. Altogether, our results illustrate that Bag5 overexpression sustains endothelial cell survival in response to catecholamine treatment. This finding identifies Bag5 downregulation and the inactivated MAPK–ERK pathway as potential mechanisms underlying catecholamine‐induced endothelial cell damage.     

Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines

Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.