Differential control of tyrosine hydroxylase activation and catecholamine secretion by voltage-operated Ca2+ channels in bovine chromaffin cells.
Contributions of L-, N-, and P/Q-type voltage-operated Ca2+ channels to two responses of bovine adrenal chromaffin cells have been studied using the nonreceptor stimulus K+ depolarization. Tyrosine hydroxylase activity and catecholamine secretion were both increased by K+ over a similar concentration range and in a Ca(2+)-dependent manner. At a submaximal concentration of 20 mM K+, tyrosine hydroxylase activation was reduced by nitrendipine but unaffected individually by (+/-)-Bay K 8644, omega-conotoxin GVIA, omega-agatoxin IVA, and omega-conotoxin MVIIC. It was fully blocked by combined inhibition of L-, N-, and P/Q-type channels. With a maximal concentration of 50 mM K+, tyrosine hydroxylase activation was unaffected by nitrendipine as well as by each of the other drugs on its own; however, it was reduced by 71 % by combined inhibition of L-, N-, and P/Q-type channels. In contrast, catecholamine secretion with both 20 and 50 mM K+ was enhanced by (+/-)-Bay K 8644, partially inhibited by nitrendipine and omega-conotoxin MVIIC, and completely blocked by a combination of antagonists for L-, N-, and P/Q-type channels. The results show that Ca2+ entry through voltage-operated Ca2+ channels can differentially regulate distinct chromaffin cell responses and that this is an intrinsic property of the mechanisms by which Ca2+ entry activates these responses. It is not dependent on the parallel activation of other signaling events by receptors.
O'Farrell
M
M
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Marley
P D
PD
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000201:enzymology / Q000378:metabolism*; D004594:Electrophysiology; D004837:Epinephrine / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014446:Tyrosine 3-Monooxygenase; D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine