Effects of Bay K 8644 and other dihydropyridines on basal and potassium-evoked output of MSH from mouse melanotrophs in vitro.
Dihydropyridines that have been shown in studies on other tissues either to facilitate Ca influx (BAY K 8644) or depress it (nimodipine and nifedipine) were examined for their effects on the secretory activity of the melanotrophs. Isolated mouse neurointermediate lobes, cultured for a week or longer to allow the nerves to degenerate, were perifused and output of MSH activity was measured by bioassay. The Ca-channel agonist BAY K 8644 augmented secretion under basal conditions and potentiated secretion evoked by 30 mM K+, a submaximally depolarizing concentration. The stimulant effect on secretion under basal conditions persisted in the presence of tetrodotoxin (which blocks the action potentials, Na spikes, in the melanotrophs) but was lost when Ca2+ was omitted or nimodipine added. The results are considered to support the view that the prominent basal secretory activity in these cells, as well as that evoked by excess K+, involve the inward flux of Ca2+ through dihydropyridine-sensitive Ca channels. If the stimulant and inhibitory effects of the dihydropyridines on basal secretion are to be attributed to actions on voltage-regulated Ca channels, as the results from other tissues would suggest, then such channels in the melanotrophs are different from those previously described in other tissues.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D004347:Drug Interactions; D007473:Ion Channels / Q000502:physiology; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism*; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*
D007473:Ion Channels; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009074:Melanocyte-Stimulating Hormones; D009543:Nifedipine; D011188:Potassium; D002118:Calcium