title: Activation of growth hormone secretagogue type 1a receptor inhibits T-type Ca2+ channel currents through pertussis toxin-sensitive novel protein kinase C pathway in mouse spermatogenic cells.
abstract: Ghrelin, a newly isolated brain-gut peptide, has been found to play important roles in the male reproduction. However, to date, the detailed mechanisms still remain unknown. In this study, we identified a novel functional role of ghrelin in modulating T-type Ca(2+) channel currents (T-currents) in mouse spermatogenic cells. We found that ghrelin inhibited T-currents in a dose-dependent manner. Ghrelin at 0.1 μM reversibly inhibited T-currents by ∼31.7%. This inhibitory effect was blocked by D-Lys3-GHRP-6, a selective growth hormone secretagogue receptor 1a (GHS-R1a) antagonist. Intracellular infusion of GDP-b-S or pretreatment of the cells with pertussis toxin (PTX) completely blocked the inhibitory effects of ghrelin. Furthermore, ghrelin responses were abolished by the phospholipase C inhibitor U73122, but not the inactive analogue U73343. The classical and novel protein kinase C antagonist chelerythrine chlorid or GF109203X abolished ghrelin responses, whereas Ro31-8820, a classical PKC antagonist or PKI 6-22, a PKA antagonist, elicited no such effects. Taken together, these results suggest that ghrelin acting through GSH-R1a inhibits T-currents via a PTX-sensitive novel PKC pathway in mouse spermatogenic cells, which could contribute to its male reproductive functions such as acrosome reactions.
authors.affiliation: Department of Neurology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, P.R. China.
authors.forename: Kangyong
authors.initials: K
authors.lastname: Liu
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Jiang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Tao
authors.forename: Liwei
authors.initials: L
authors.lastname: Shen
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Sun
mesh_terms: D000177:Acrosome / Q000378:metabolism; D020101:Acrosome Reaction; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D054439:Ghrelin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013093:Spermatogonia / Q000166:cytology* / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D020747:Calcium Channels, T-Type; D004963:Estrenes; C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D009842:Oligopeptides; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D054440:Receptors, Ghrelin; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium