title: Effects of the potassium channel openers cromakalim and pinacidil on catecholamine secretion and calcium mobilization in cultured bovine adrenal chromaffin cells.
abstract: The effects of two K+ channel openers, cromakalim and pinacidil, on voltage-dependent and receptor-mediated catecholamine secretion and Ca2+ mobilization in bovine adrenal chromaffin cells were studied to determine the role of membrane K+ channels in the regulation of a Ca(2+)-dependent secretory process. Both cromakalim and pinacidil stimulated the efflux of 86Rb (used to monitor K+ permeability) from preloaded cells. Cromakalim and pinacidil did not affect the catecholamine secretion induced by excessive depolarization with 56 mM K+, but inhibited that induced by moderate depolarization with 31 mM K+ in a concentration-dependent manner (1 microM-100 microM). The 31 mM K(+)-induced 45Ca2+ influx and increase in intracellular free Ca2+ concentration [Ca2+]i were also inhibited by these agents at similar concentrations to those for inhibition of catecholamine secretion. Cromakalim and pinacidil inhibited catecholamine secretion, 45Ca2+ influx and increase in [Ca2+]i induced by stimulation of nicotinic acetylcholine (ACh) receptors with carbamylcholine. Furthermore, both cromakalim and pinacidil inhibited the increase in [Ca2+]i induced by carbamylcholine in the absence of extracellular Ca2+, which is thought to be mediated by muscarinic ACh receptors. On the other hand, they did not affect catecholamine secretion induced by Bay-K 8644, Ba2+, A23187, histamine or bradykinin. These results indicate that the K+ channel openers, cromakalim and pinacidil, selectively inhibit catecholamine secretion induced by moderate depolarization or by nicotinic ACh receptor stimulation by inhibiting Ca2+ influx and increase in [Ca2+]i. Furthermore, the results suggest that these K+ channel openers-sensitive membrane K+ channels are involved in the regulation of catecholamine secretion mainly indirectly through effects on the voltage-dependent membrane Ca2+ channels.
authors.affiliation: Department of Pharmacology, Tokushima University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Masuda
authors.forename: M
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: Y
authors.initials: Y
authors.lastname: Ishimura
authors.forename: I
authors.initials: I
authors.lastname: Katoh
authors.forename: M
authors.initials: M
authors.lastname: Oka
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019806:Cromakalim; D006146:Guanidines / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D020110:Pinacidil; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D012414:Rubidium Radioisotopes
chemical_list: D001578:Benzopyrans; D002395:Catecholamines; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D019806:Cromakalim; D001464:Barium; D000001:Calcimycin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020110:Pinacidil; D006632:Histamine; D002217:Carbachol; D011188:Potassium; D001920:Bradykinin; D002118:Calcium