GHRP6-stimulated hormone secretion in somatotrophs: involvement of intracellular and extracellular calcium sources.
GHRP6 is a synthetic hexapeptide which stimulates growth hormone (GH) secretion from the pituitary in vivo and in vitro. We have previously shown that in identified somatotrophs, GHRP6 induces a biphasic increase in cytosolic Ca2+ concentration ([Ca2+]i) consisting of an abrupt increase (first phase) followed by a sustained plateau of elevated [Ca2+]i (second phase). The first phase corresponds to mobilization of intracellular Ca2+ pools and the second phase to influx of extracellular Ca2+ ions through voltage-sensitive Ca2+ channels. In these experiments, we investigated the specific role of each of these two phases in the hormone response to GHRP6. We found that inhibition by thapsigargin of the intracellular Ca2+ mobilization phase significantly inhibited the hormone response to the peptide during 30 min incubations. Inhibition of the extracellular Ca2+ influx phase by nifedipine, a blocker of voltage-sensitive Ca2+ channels, resulted in a 53 percent reduction of the secretory response to 10(-5)M GHRP6. Antagonism of PKC by phloretin, a flavonoid which prevents PKC activation, and PKC depletion induced by a 24 h treatment with 10(-6)M PMA, completely inhibited the response to GHRP6. Somatostatin, which also inhibits the second phase of the Ca2+ response, suppressed the secretory response to GHRP6. We conclude that, Ca2+ is the main second messenger and both Ca2+ mobilization and Ca2+ entry play a role in the response to GHRP6. However, experiments with PKC depletion and SRIF suggest that other messengers are implicated in GHRP6 signalling in somatotrophs.
Bresson-Bepoldin
L
L
Laboratoire de Neurophysiologie, Universite de Bordeaux, France.
Dufy-Barbe
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L
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000494:pharmacology
D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D011493:Protein Kinase C; D002118:Calcium