Role of voltage-sensitive calcium channels in [Ca2+]i and secretory responses to activators of protein kinase C in pituitary gonadotrophs.
The gonadotropin secretory response of anterior pituitary cells to phorbol esters includes both extracellular Ca2(+)-dependent and -independent components (Stojilković et al, 1988; J. Biol. Chem. 263, 17301-17306, 1988). In cultured pituitary cells, measurements of [Ca2+]i using Fura-2 and of LH release during cell perifusion studies revealed that the initial effects of phorbols and permeant diacylglycerols on these responses are extracellular Ca2(+)-dependent and are mediated through activation of voltage- and dihydropyridine-sensitive calcium channels. On the other hand, pretreatment with phorbol esters for 30 to 60 min inhibited subsequent [Ca2+]i responses to diacylglycerols and phorbols and significantly reduced agonist-induced biphasic [Ca2+]i responses, with no change in the number of GnRH receptors. These findings demonstrate that protein kinase C exerts both positive and negative control of [Ca2+]i, and indicate that the calcium, phospholipid dependent enzyme participates in the activation of voltage-sensitive calcium channels and hormone secretion in pituitary gonadotrophs.
Izumi
S
S
Endocrinology and Reproduction Research Branch, National Institutes of Child Health and Human Development, NIH, Bethesda, Maryland 20892.
Stojilković
S S
SS
Iida
T
T
Krsmanović
L Z
LZ
Omeljaniuk
R J
RJ
Catt
K J
KJ
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology; D004594:Electrophysiology; D004789:Enzyme Activation; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism*; D010052:Ovariectomy; D010703:Phorbol Esters / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D010906:Pituitary Hormone-Releasing Hormones / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats
D015220:Calcium Channels; D004075:Diglycerides; D010703:Phorbol Esters; D010906:Pituitary Hormone-Releasing Hormones; D007986:Luteinizing Hormone; D011493:Protein Kinase C; D002118:Calcium