Colchicine inhibits adrenal medullary secretion evoked by acetylcholine without affecting that evoked by potassium

Douglas, W. W.; Sorimachi, Masaru

doi:10.1111/j.1476-5381.1972.tb09585.x

Cited by 74 publications

(26 citation statements)

References 20 publications

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“…Colchicine interferes with the exocytotic secretion of many hormones (Lacy, Howell, Young & Fink, 1968;Kraicer & Milligan, 1971;Douglas & Sorimachi, 1972;Sorimachi, Oesch & Thoenen, 1973) possibly by causing disintegration of microtubules (Borisy & Taylor, 1967). In the present experiments, responses to 5-HT and DMPP, but not those to noradrenaline or tyramine, were inhibited by colchicine (Figure 3).…”

Section: Discussionsupporting

confidence: 53%

Mechanism of the Indirect Sympathomimetic Effect of 5‐hydroxytryptamine on the Isolated Heart of the Rabbit

Fozard

Mwaluko

1976

British J Pharmacology

142

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1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethylphenylpiperazinium (DMPP). 2 The cardiac stimulant effects of 5-HT, tyramine and DMPP were inhibited by propranolol and practolol and the pA2 values obtained were similar to those obtained with noradrenaline as the agonist. 3 Responses to 5-HT, tyramine and DMPP were greatly reduced on hearts from rabbits pretreated with 6-hydroxydopamine. Such hearts had less than 7% of their normal catecholamine concentration and no fluorescence characteristic of noradrenaline in the cardiac sympathetic nerves could be demonstrated. 4 Rapid, reversible and selective tachyphylaxis to 5-HT was demonstrated during perfusion with 5-HT. In hearts desensitized to DMPP by perfusion with DMPP, responses to 5-HT were also reduced. S Perfusion of hearts with colchicine inhibited stimulant responses to 5-HT and DMPP but had little effect on responses to noradrenaline or tyramine. 6 Desmethylimipramine enhanced cardiac stimulant responses to noradrenaline and to a lesser extent, those to 5-HT and DMPP. Responses to tyramine were consistently inhibited by desmethylimipramine. 7 Tetrodotoxin abolished responses of the heart to electrical nerve stimulation but left responses to noradrenaline, 5-HT and DMPP unaffected. 8 5-HT, tyramine and DMPP evoked 3H-release from hearts whose neuronal noradrenaline stores had been labelled by perfusion with [3HI-(-)-noradrenaline. The pattern of release evoked by 5-HT was similar to that of DMPP but differed from that of tyramine.9 Reducing the calcium concentration in the Tyrode solution from 3.6 to 0.2 mEq/l did not affect 3H-overflow after tyramine but greatly inhibited that evoked by 5-HT and DMPP.10 The results confirm that the stimulant effects of 5-HT on the rabbit isolated heart are the result of noradrenaline release. They further suggest that the site of the release is the terminal sympathetic nerve network. The mechanism of release shows more similarities to that of DMPP (calcium-dependent depolarization and exocytosis) than to that of tyramine (neuronal uptake and stoichiometric displacement).

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Section: Discussionsupporting

confidence: 53%

Mechanism of the Indirect Sympathomimetic Effect of 5‐hydroxytryptamine on the Isolated Heart of the Rabbit

Fozard

Mwaluko

1976

British J Pharmacology

142

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“…If the site of action were microtubules, one might expect an inhibition of K+-stimulated release because both K+ and ACh are thought to induce secretion by a common pathway involving exocytosis. It is interesting that vinblastine has different effects on ACh-and K+-stimulated release (23,24), and this may be related to the parallel differences we observed between ACh and excess K+ with regard to calcium dependence and tetracaine block of secretion. (See note added in proof.…”

Section: Resultsmentioning

confidence: 99%

“…Differences between AChand K+-stimulated secretion (9,(22)(23)(24) and changes in the frequency of chromaffin cell action potentials (7) have been previously noted. Brandt et al (7) demonstrated that an increased action potential spike frequency (2.5/sec) could be maintained as long as 10,uM ACh was present in the medium, whereas 15.6 mM K+ was only able to increase the spike frequency for about a minute, after which it dropped by an order of magnitude to spontaneous spike frequencies of about 0.1/sec.…”

Section: Resultsmentioning

confidence: 99%

Stimulus-secretion coupling in chromaffin cells isolated from bovine adrenal medulla

Schneider¹,

Herz²,

Rosenheck³

1977

Proc. Natl. Acad. Sci. U.S.A.

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Bovine adrenal chromaffin cells were isolated by removal of the cortex and sequential collagenase digestion of the medulla. The catecholamine secretory function of these cells was characterized with respect to acetylcholine stimulation, cation requirements, and cytoskeletal elements. The dose-response curve for stimulated release had its half-maximum value at 10-5 M acetylcholine, and maximum secretion was on the average 7 times that of control basal secretion. The differential release of epinephrine versus norepinephrine after stimulation with 0.1 mM acetylcholine occurred in proportion to their distribution in the cell suspension. The cholinergic receptors were found to be predominantly nicotinic. The kinetics of catecholamine release were rapid, with significant secretion occurring in less than 60 sec and 85% of maximum secretion within 5 min. A critical requirement for calcium in the extracellular medium was demonstrated, and 80% of maximum secretion was achieved at physiologic calcium concentrations. Stimulation by excess potassium (65 mM KCI) also induced catecholamine secretion which differed from acetylcholine stimulation in being less potent, in having a different dependence on calcium concentration, and in its response to the local anesthetic tetracaine. Tetracaine, which is thought to inhibit membrane cation permeability, was able to block acetylcholine-stimulated but not KCI-stimulated secretion. The microtubule disrupting agent vinblastine was able to block catecholamine release whereas the microfilament disrupter cytochalasin B had little effect. The results show the isolated bovine chromaffin cells to be viable, functioning, and available in large quantity. These cells now provide an excellent system for studying cell surface regulation of hormone and neurotransmitter release.The term "stimulus-secretion coupling" was originally coined by Douglas and Rubin (1, 2) more than a decade ago to describe the sequence of events initiated by acetylcholine (ACh) stimulation of adrenal chromaffin cells and leading to secretion of catecholamines by exocytosis. They had in mind the close similarity to the phenomenon of "excitation-contraction coupling" in muscle (namely, the key role of calcium in mediating both secretion and contraction and a parallel set of electrical and ionic events at the plasma membrane in response to ACh). Much progress has been made during the past 2 decades in elucidating the various steps in the mechanism of secretion, with a substantial portion of the data deriving from studies on the perfused adrenal gland (2-4). There remain, however, many important aspects of cell surface receptor regulation of secretion that are still poorly understood, such as (i) the molecular nature of the calcium permeability sites that are altered by activated cholinergic receptors and potassium depolarization, (ii) the mechanism by which calcium entry into the cell induces membrane fusion and exocytosis, (iii) the possible role of cyclic nucleotides coupled with ion translocation in mediating horm...

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“…Among these actions is the ability of colchicine to modify the behaviour of membrane proteins (Wunderlich et al, 1973). In earlier work in which colchicine was used to study adrenal medullary secretion evoked by activation of the acetylcholine receptor, the proposal was advanced that its action was exerted at an early step of the stimulus-secretion coupling (Douglas & Sorimachi, 1972). Recent work on this subject has shown that colchicine specifically inhibits the acetylcholine receptor-mediated stimulation of G protein GTPase activity (Ravindra & Aronstami, 1990).…”

Section: Discussionmentioning

confidence: 99%

Modulation of the hepatic α¹‐adrenoceptor responsiveness by colchicine: dissociation of free cytosolic Ca²⁺‐dependent and independent responses

Butta

Martín-Requero

Urcelay

et al. 1996

British J Pharmacology

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1 The cytoskeletal depolymerizing agent, colchicine, prevents the hepatic ax-adrenoceptor-mediated stimulation of respiration, H+ and Ca2+ release to the effluent perfusate, intracellular alkalosis, and glycogenolysis. Unlike the other parameters, colchicine does not perturb the a,-agonist-induced stimulation of gluconeogenesis or phosphorylase 'a' activation, and enhances the increase in portal pressure response. The lack of effect of colchicine on the hepatic a2-adrenoceptor-mediated effects indicates that its actions are a,-specific.2 Colchicine enhances the acute ax-adrenoceptor-mediated intracellular Ca21 mobilization and prevents the activation of protein kinase C. This differential effect on the two branches of the a1-adrenoceptor signalling pathway is a distinctive feature of the colchicine action.3 The lack of effect of colchicine in altering the ax-adrenoceptor ligand binding affinity suggests that it might interact with some receptor-coupled regulatory element(s). 4 The acuteness of the colchicine effect and the ability of its isomer fl-lumicolchicine to prevent all the ac-adrenoceptor-mediated responses but the increase in vascular resistance, indicate that its action cannot be merely ascribed to its effects in depolymerizing tubulin. 5 Colchicine perturbs the hepatic responses to vasoactive peptides. It enhances the vasopressin-induced rise of cytosolic free Ca2+ in isolated hepatocytes and prevents the sustained decrease of Ca2+ in the effluent perfusate. It also inhibits the stimulation of glycogenolysis, without altering the stimulation of gluconeogenesis.6 It is concluded that there are at least two major a1-adrenoceptor signalling pathways. One is colchicine-sensitive, independent of variations in free cytosolic Ca2+, and protein kinase C-dependent; the other one is colchicine-insensitive, dependent on variations in free cytosolic Ca2", and protein kinase C-independent.

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Colchicine inhibits adrenal medullary secretion evoked by acetylcholine without affecting that evoked by potassium

Cited by 74 publications

References 20 publications

Mechanism of the Indirect Sympathomimetic Effect of 5‐hydroxytryptamine on the Isolated Heart of the Rabbit

Mechanism of the Indirect Sympathomimetic Effect of 5‐hydroxytryptamine on the Isolated Heart of the Rabbit

Stimulus-secretion coupling in chromaffin cells isolated from bovine adrenal medulla

Modulation of the hepatic α¹‐adrenoceptor responsiveness by colchicine: dissociation of free cytosolic Ca²⁺‐dependent and independent responses

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Colchicine inhibits adrenal medullary secretion evoked by acetylcholine without affecting that evoked by potassium

Cited by 74 publications

References 20 publications

Mechanism of the Indirect Sympathomimetic Effect of 5‐hydroxytryptamine on the Isolated Heart of the Rabbit

Mechanism of the Indirect Sympathomimetic Effect of 5‐hydroxytryptamine on the Isolated Heart of the Rabbit

Stimulus-secretion coupling in chromaffin cells isolated from bovine adrenal medulla

Modulation of the hepatic α1‐adrenoceptor responsiveness by colchicine: dissociation of free cytosolic Ca2+‐dependent and independent responses

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Modulation of the hepatic α¹‐adrenoceptor responsiveness by colchicine: dissociation of free cytosolic Ca²⁺‐dependent and independent responses