Inhibition of catecholamine release from the adrenal medulla by halothane

Abstract

In isolated bovine adrenals perfused with Locke solution in a retrograde fashion we investigated the effects of halothane on the catecholamine release evoked by various secretagogues. 1. The catecholamine release induced by activation of the nicotinic receptors on the chromaffin cells with 1,1-dimethyl-4-phenylpiperazinium was almost completely inhibited (by about 90%) by 1.4 X 10(-3) M halothane. 2. It was shown by means of cumulative concentration-response curves of acetylcholine for its stimulating effect on catecholamine release (pD2 = 4.04) that halothane was a non-competitive antagonist (pD'2 = 3.17). 3. Halothane (1.4 X 10(-3) and 4.3 X 10(-3) M) did not decrease the catecholamine secretion in response to pilocarpine or histamine. 4. The 5-hydroxytryptamine-induced catecholamine release was not impaired by 1.4 X 10(-3) M halothane, but was significantly inhibited (by 44%) by 4.3 X 10(-3) M halothane. 5. At 1.4 X 10(-3) M halothane the catecholamine release induced by gamma-aminobutyric acid (GABA) was inhibited by 40%. 4.3 X 10(-3) M halothane completely blocked the secretion induced by GABA. 6. The catecholamine secretion in response to 56 mM KCl or to introduction of CaCl2 after perfusion with Locke solution deficient in CaCl2 was not reduced by halothane (1.4 X 10(-3) and 1.4 X 10(-2) M). 7. Halothane (1.4 X 10(-3) M) did not inhibit the catecholamine release evoked by acetaldehyde or tyramine from glands perfused with Ca2+ -free Locke solution throughout the experiments. It is concluded that the site of action of halothane is the cell membrane of the chromaffin cell. The anaesthetic does not impair the permeability of the membrane to calcium ions. Halothane may cause a conformational change of membrane proteins, particularly of the nicotinic receptor (and at higher concentrations of GABA and 5-hydroxytryptamine receptors); thus, stimulation may be prevented by an inhibition of agonist-receptor interaction.

The effects of inhalation anesthetics on calcium-stimulated exocytosis in a natural membrane model system

“…However, in the presence of excess calcium, each of the examined anesthetics inhibited exocytosis to some extent. These results are generally consistent with prior studies showing that volatile anesthetics inhibit secretory processes in intact cells (Pocock and Richards, 1986;Cheek et al, 1986;Sumikawa et al, 1985;Bosnjak et al, 1982;Gothert et al, 1976) and provide experimental support for our hypothesis that halothane inhibits the formation of the echinoderm fertilization envelope by impairing the Ca2+-regulated fusion of cortical vesicles with the egg plasma membrane (Hinkley and Wright, 1986). Although our 9-10) at 22 ° .…”

“…These observations, in conjunction with the present data, suggest that exocytotic events in intact cells are more sensitive to anesthetics than those of isolated membrane (cortex) preparations. Supporting this notion, clinical concentrations of halothane have been reported to inhibit secretory events in intact chromaffin cells of the adrenal medulla (Pocock and Richards, 1986;Sumikawa et al, 1985;Gothert et al, 1976), mast cells in organ culture (Cheek at al., 1986), and explanted sympathetic ganglia (Bosnjak et al, 1982). A plausible explanation for the differences in anesthetic sensitivity observed between intact sea urchin eggs and isolated cortices is that volatile anesthetics may inhibit exocytosis by affecting some regulatory component or pathway (see below) which is partially inactivated or perhaps not well preserved in isolated cortices.…”

“…Studies in which the products secreted by intact cells have been measured generally support the conclusion that volatile anesthetics inhibit the fusion of secretory vesicles with the plasma membrane of a variety of cell types including chromaffin cells (Pocock and Richards, 1986;Sumikawa et al, 1985;Gothert et al, 1976), mast cells (Cheek at al., 1986), and even sympathetic neurons (Bosnjak et al, 1982). Paradoxically, recent studies clearly show that inhalati0nal anesthetics actually enhance the.…”

The action of volatile anaesthetics on stimulus‐secretion coupling in bovine adrenal chromaffin cells

“…Moreover, volatile anaesthetics are known to inhibit catecholamine secretion from adrenal glands both in vivo and in vitro (Gothert et al, 1976;Gothert & Wendt, 1976). For these reasons, chromaffin cells offer a suitable experimental model for the analysis of the action of anaesthetics on neurosecretion.…”

Inhibitory effects of propofol on catecholamine secretion and uptake in cultured bovine adrenal medullary cells

“…Of the three ion channels in adrenal medullary cells general anaesthetics, such as enflurane (G6thert and Wendt 1977), ketamine (Takara et al 1986), halothane (G6thert et al 1976;Yashima et al 1986) and isoflurane , have been shown to inhibit most strongly the nicotinic acetylcholine receptor-associated ion channels. The order of potency of the inhibitory effect by these anaesthetics is: nicotinic actylcholine receptor-associated ion channels > voltage-dependent Na + channels >> voltage-dependent Ca 2 ÷ channels (Yashima et al 1986;Takara et al 1986.…”