Ghrelin and GHRP-6 enhance electrical and secretory activity in GC somatotropes.
It is well established that pituitary somatotropes fire spontaneous action potentials (SAP) which generate Ca(2+) signals of sufficient amplitude to trigger growth hormone (GH) release. It is also known that ghrelin and synthetic GH-releasing peptides (GHRPs) stimulate GH secretion, though the mechanisms involved remain unclear. In the current report, we show that the chronic (96h) treatment with ghrelin and GHRP-6 increases the firing frequency of SAP in the somatotrope GC cell line. This action is associated with a significant increase in whole-cell inward current density. In addition, long-term application of Na(+) or L-type Ca(2+) current antagonists decreases GHRP-6-induced release of GH, indicating that the ionic currents that give rise to SAP play important roles for hormone secretion in the GC cells. Together, our results suggest that ghrelin and GHPR-6 may increase whole-cell inward current density thereby enhancing SAP firing frequency and facilitating GH secretion from GC somatotropes.
Dominguez
Belisario
B
Laboratory of Neuroendocrinology, Institute of Physiology, University of Puebla, Puebla, Mexico.
Felix
Ricardo
R
Monjaraz
Eduardo
E
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism*; D015640:Ion Channel Gating; D009543:Nifedipine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D036361:Peptide Hormones / Q000494:pharmacology*; D010911:Pituitary Neoplasms; D051381:Rats; D011986:Receptors, Somatotropin / Q000378:metabolism; D052683:Somatotrophs / Q000187:drug effects* / Q000502:physiology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D054439:Ghrelin; D009842:Oligopeptides; D036361:Peptide Hormones; D011986:Receptors, Somatotropin; C041048:growth hormone releasing hexapeptide; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D013006:Growth Hormone; D009543:Nifedipine