Mechanism of the inhibitory effect of thiopentone on stimulus-secretion coupling in chromaffin cells.
This study was undertaken to clarify the mechanism of action of thiopentone on stimulus-secretion coupling in cholinergic postsynaptic cells using cultured bovine adrenal chromaffin cells. Thiopentone (20-100 microns) inhibited carbachol-induced Ca2+ uptake into, and catecholamine release from the cells in a concentration-dependent manner. The inhibition of catecholamine release was almost parallel to the inhibition of Ca2+ uptake. The inhibitory effect of thiopentone was not overcome by an increase in the concentration of carbachol, whereas that of alcuronium was. Contrary to the inhibition by diltiazem, which was reversed by increasing the Ca2+ concentration, the inhibition by thiopentone was not overcome by a high Ca2+ concentration. Compared with the inhibition of carbachol-induced catecholamine release, a higher concentration of thiopentone was required to inhibit high K+ (56 mM KCl)-induced catecholamine release (200 microns thiopentone exhibited 32% inhibition). The results suggest that thiopentone blocks the stimulus-secretion coupling in the chromaffin cells as a result of inhibiting Ca2+ uptake through nicotinic receptor-linked channels. The linkage between receptor stimulation and Ca2+ channel activation seems to be the process most susceptible to inhibition by the barbiturate.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D013874:Thiopental / Q000494:pharmacology*
D002395:Catecholamines; D007473:Ion Channels; D002217:Carbachol; D013874:Thiopental; D002118:Calcium