Inhibition of 45Ca2+ uptake and catecholamine secretion by phenothiazines and pimozide in adrenal medulla cells cultures.
The inhibition by several phenothiazine drugs and pimozide of the uptake of 45Ca2+ and secretion of catecholamines by cultured adrenal medulla cells stimulated with nicotine, veratridine, 50 mM K+, ionomycin and Ba2+ was studied. The inhibition of 45Ca2+ uptake, except for ionomycin, closely parallelled the inhibition of catecholamine secretion. The nicotine-and veratridine-stimulated effects were several fold more sensitive to inhibition by the drugs than were those stimulated by 50mM K+, ionomycin and Ba2+; the ionomycin-stimulated effects were least sensitive to inhibition. These studies indicate that the drugs have multiple effects on stimulus-secretion coupling in adrenal medulla cells. It is suggested that inhibition of the veratridine- and nicotine-stimulated events is due to membrane perturbations caused by the drugs, that inhibition of the 50mM K+- and Ba2+-stimulated events is due to alterations in the voltage sensitive membrane Ca2+ channel, and that inhibition of secretion elicited by ionomycin may be due to inhibition of Ca2+-calmodulin reactions or to more profound non specific membrane effects.
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004987:Ethers / Q000494:pharmacology; D015759:Ionomycin; D009538:Nicotine / Q000494:pharmacology; D010640:Phenothiazines; D010868:Pimozide / Q000494:pharmacology*; D014701:Veratridine / Q000494:pharmacology
D014150:Antipsychotic Agents; D002132:Calcium Radioisotopes; D002395:Catecholamines; D004987:Ethers; D010640:Phenothiazines; D010868:Pimozide; D015759:Ionomycin; D009538:Nicotine; D014701:Veratridine; D002118:Calcium