Effect of Colchicine on<i>in Vitro</i>ACTH Release Induced by High K<sup>+</sup>and by Hypothalamus-Stalk-Median Eminence Extract

Kraicer, Jacob; Milligan, John V.

doi:10.1210/endo-89-2-408

Cited by 54 publications

(14 citation statements)

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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: 44%

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: 44%

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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“…Lacy, Howell, Young & Fink (1968) suggested that microtubules, or like elements, may be involved in secretion of insulin by emiocytosis (exocytosis) and supported their concept with evidence that colchicine, a drug whose disrupting actions on microtubules is well documented (Borisy & Taylor, 1967), depressed the output of insulin from pancreatic /3-cells stimulated, in vitro, with glucose (see also MalaisseLagae, Greider, Malaisse & Lacy, 1971). Experiments on other secretory cells, stimulated by various means, have not always revealed such sensitivity to colchicine (Kraicer & Milligan, 1971;Schofield & Cole, 1971), but where significant inhibition has been observed this has generally been considered as support for the involvement of microtubules or related elements (Gillespie, Levine & Malawista, 1968;Kraicer & Milligan, 1971;Levy & Carlton, 1971;Schofield & Cole, 1971 (1961) as modified by Sorimachi (1968). Catecholamines were assayed by the fluorometric method according to Anton & Sayre (1962).…”

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confidence: 99%

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

Douglas

Sorimachi

1972

British J Pharmacology

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“…Since Lacy et al suggested that the microtubular system in the islet cells of the pancreas probably plays an important role in the secretion of insulin from these cells (2), several in vitro experiments have been carried out on the pituitary, thyroid and adrenal glands concerning the influence of colchicine and other antimicrotubular agents on endocrine functions (3)(4)(5)(6)(7)(8). A consensus of opinion, however, has never been reached, and few in vivo experiments clarifying the effect of colchicine and other antimicrotubular agents on adrenocortical function have been documented.…”

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confidence: 99%

Effect of Colchicine on Steroid Secretion From Rat Adrenal Gland

Inaba

Kamata

1979

Japanese Journal of Pharmacology

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Abstract-To determine the influence of colchicine on adrenocortical function in vivo, we gave significant amounts subcutaneously to rats and observed the distribution to the anterior pituitary and adrenal glands. Corticosteroids in the serum and adrenal gland were increased remarkably by the administration of colchicine in a dose-dependent manner.Maximum elevation was achieved around 2.5 hours after the injection and continued for at least 4 hours. Maximum levels produced by the injection of 1 mg/kg body wt. of colchicine were the same as those elicited by the injection of 0.1 U/rat of adrenocorticotropic hormone, the latter producing temporary increases in corticos teroids in the serum and adrenal gland. A significant augmentation of corticosteroids in the serum and adrenal gland resulted when colchicine was administered 60 minutes prior to the injection of adrenocorticotropic hormone. The pattern of intracellular distribution of corticosteroids in the adrenal glands of rats given colchicine was the same as that seen in rats given adrenocorticotropic hormone. In the in vitro experiment, only high concentrations of colchicine such as 10-3 M added to the incubation system of the adrenal quarters suppressed the release of corticosteroids from the adrenal gland. Thus, the continuous stimulation of the synthesis and secretion of adrenocortical hormone seen with the administration of colchicine may explain why this drug is effective in the treatment of gouty arthritis.Colchicine has long been effectively used for cases in acute gouty arthritis, but the mode of action is not entirely understood. A possible relationship between the genesis of acute gouty arthritis and inflammatory reaction of the knee joint produced by the local injection of urate crystals has been suggested (1), but colchicine administration does not produce a decrease in the concentration of uric acid in the serum or promote the excretion of uric acid. The present study was carried out to examine the influence of colchicine administration on adrenocortical function in rats in vivo. Direct effect of the agent on the release of corti costeroids from adrenal gland was also studied in the in vitro experiment.

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Effect of Colchicine onin VitroACTH Release Induced by High K⁺and by Hypothalamus-Stalk-Median Eminence Extract

Cited by 54 publications

References 0 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

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

Effect of Colchicine on Steroid Secretion From Rat Adrenal Gland

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Effect of Colchicine onin VitroACTH Release Induced by High K+and by Hypothalamus-Stalk-Median Eminence Extract

Cited by 54 publications

References 0 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

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

Effect of Colchicine on Steroid Secretion From Rat Adrenal Gland

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Effect of Colchicine onin VitroACTH Release Induced by High K⁺and by Hypothalamus-Stalk-Median Eminence Extract