Effects of acetylcholine and other medullary secretagogues and antagonists on the membrane potential of adrenal chromaffin cells: an analysis employing techniques of tissue culture

Douglas, W. W.; Kanno, Tomio; Sampson, Sanford R.

doi:10.1113/jphysiol.1967.sp008127

Cited by 189 publications

(63 citation statements)

References 24 publications

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“…Indeed, Sonenberg and Schneider (25) have recently proposed a model of hormone action that draws heavily on analogy to neurotransmitter mechanisms and includes both an anionic and a cyclic nucleotide response. For the chromaffin cell and ACh receptor system there already exists an important body of information on membrane electric potential and ion permeability changes (5)(6)(7)(8). There are also recent data on the adrenal medulla and related systems, including postganglionic sympathetic neurons, demonstrating an elevation in cyclic nucleotides in response to ACh (26,27).…”

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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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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“…Pilocarpine stimulates chromaffin cells (Douglas, Kanno & Sampson, 1967), but not sympathetic nerve endings in the heart (Haeusler et al, 1968). The finding that pilocarpine differed from other muscarinic cholinomimetics in that it enhanced but did not depress responses to sympathetic nerve stimulation may be related to the difference between its effects and those of other muscarinic substances on ganglion cells (Takeshige & Volle, 1964).…”

Section: Discussionmentioning

confidence: 99%

The effects of cholinomimetic drugs on responses to sympathetic nerve stimulation and noradrenaline in the rabbit ear artery

Rand

Varma

1970

British J Pharmacology

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Summary1. The effects of infusions of the cholinomimetic drugs acetylcholine, methacholine, muscarine, carbachol, arecoline and pilocarpine were examined on vasoconstrictor responses of the perfused rabbit ear artery to sympathetic nerve stimulation and to injections of noradrenaline.2. The first effect of very low concentrations of acetylcholine or muscarine was a slight enhancement of responses to sympathetic nerve stimulation, but when higher concentrations of acetylcholine, methacholine, muscarine, carbachol and arecoline were infused, these vasoconstrictor responses were decreased.With still higher concentrations the responses tended to increase in size during the infusion. After stopping an infusion, the depressed vasoconstrictor responses rapidly recovered and became enhanced. 3. Infusions of pilocarpine in a wide range of concentrations generally caused enhancement of responses. 4. The depressant effects of cholinomimetic drugs on the responses to sympathetic nerve stimulation were antagonized by atropine. Larger concentrations of the drugs overcame the blockade by atropine. 5. The effects of acetylcholine, methacholine and muscarine on the responses to sympathetic nerve stimulation were more pronounced at low than at high frequencies of stimulation. 6. Vasoconstrictor responses to injected noradrenaline were enhanced by acetylcholine or methacholine, whereas responses to sympathetic nerve stimulation were decreased by the same concentrations of these choline esters. 7. It is suggested that cholinomimetic drugs may act on receptor sites associated with the adrenergic terminal axon and that they may facilitate or impair the release of noradrenaline and impair noradrenaline uptake.

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“…In the isolated chromaffin cells of the gerbil, the depolarizing effect of pilocarpine is blocked by atropine alone; depolarization by acetylcholine is only partially blocked when hexamethonium is added alone, but completely blocked when atropine and hexamethonium are added together (Douglas, Kanno & Sampson, 1967). Atropine also blocks the depolarizing effect of acetylcholine in rat adrenal chromaffin cells (Brandt, Hagiwara, Kidokoro & Miyazaki, 1976 In isolated chromaffin cells of the bovine adrenal gland, nicotinic and muscarinic cholinoceptors have also been functionally distinguished; however, in these cells, as at the sympathetic nerve terminals, muscarinic agonists inhibit the secretory response to nicotine (Derome et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

Effect of Muscarine on Release of Catecholamines From the Perfused Adrenal Gland of the Cat

Kirpekar

Prat

Schiavone

1982

British J Pharmacology

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The secretory effect of muscarine was studied in the perfused adrenal gland of the cat. During perfusion of the adrenal gland with Krebs‐bicarbonate solution containing muscarine 480 μm, the rate of catecholamine (CA) secretion was 2.02 ± 0.43 μg/2 min in the first 2 min; thereafter, CA output declined only moderately, to reach about 70% of the initial value after 10 min. Secretory responses to brief infusions of muscarine remained reproducible for at least the first 3 infusions. When the adrenal gland was perfused with muscarine (480 μm), infusions of high K+, nicotine, or veratridine produced their usual responses. A 100 fold lower dose of muscarine also failed to modify these responses. During perfusion with high K+, muscarine evoked a secretory response that was only slightly smaller than the response to muscarine alone. It is concluded that muscarine and nicotine activate CA secretion in the cat adrenal gland by independent mechanisms and that the muscarinic response, unlike the nicotinic response, is not readily desensitized.

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Effects of acetylcholine and other medullary secretagogues and antagonists on the membrane potential of adrenal chromaffin cells: an analysis employing techniques of tissue culture

Cited by 189 publications

References 24 publications

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

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

The effects of cholinomimetic drugs on responses to sympathetic nerve stimulation and noradrenaline in the rabbit ear artery

Effect of Muscarine on Release of Catecholamines From the Perfused Adrenal Gland of the Cat

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