Suppression by phospholipase A2 inhibitors of secretion of catecholamines from isolated adrenal medullary cells by suppression of cellular calcium uptake.
The involvement of phospholipase A2 in the secretion of catecholamines and cellular uptake of 45Ca2+ was investigated in isolated bovine adrenal medullary cells. In these cells, stimulation of cholinergic receptors by carbamylcholine causes the activation of receptor-linked Ca-channels and influx of Ca2+ is known to trigger the secretory process. Phospholipase A2 inhibitors, such as quinacrine, chloroquine, quinine and p-bromophenacyl bromide, all inhibited the secretion of catecholamines evoked by carbamylcholine in a dose-dependent manner. These phospholipase A2 inhibitors also inhibited the cellular uptake of 45Ca2+ evoked by carbamylcholine with similar dose-response curves to those for inhibition of catecholamine secretion. The inhibition by phospholipase A2 inhibitors was found to be distinct from inhibition by d-tubocurarine which competitively blocks acetylcholine receptors, and from inhibition by diltiazem which acts as a Ca-antagonist at Ca-channels. Phospholipase A2 inhibitors seem to suppress the secretion of catecholamines by interfering with the linkage between acetylcholine receptors and Ca-channels by the membrane effects including the inhibition of endogenous phospholipase A2 activity of the adrenal medullary cells.
D000098:Acetophenones / Q000494:pharmacology; D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D011803:Quinine / Q000494:pharmacology
D000098:Acetophenones; D002395:Catecholamines; D002738:Chloroquine; D002217:Carbachol; D011803:Quinine; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; C006821:4-bromophenacyl bromide; D002118:Calcium