title: Ghrelin reduces voltage-gated calcium currents in GH₃ cells via cyclic GMP pathways.
abstract: Ghrelin is an endogenous growth hormone secretagogue (GHS) causing release of GH from pituitary somatotropes through the GHS receptor. Secretion of GH is linked directly to intracellular free Ca2+ concentration ([Ca2+]i), which is determined by Ca2+ influx and release from intracellular Ca2+ storage sites. Ca2+ influx is via voltage-gated Ca2+ channels, which are activated by cell depolarization. The mechanism underlying the effect of ghrelin on voltage-gated Ca2+ channels is still not clear. In this report, using whole cell patch-clamp recordings, we assessed the acute action of ghrelin on voltage-activated Ca2+ currents in GH3 rat somatotrope cell line. Ca2+ currents were divided into three types (T, N, and L) through two different holding potentials (-80 and -40 mV) and specific L-type channel blocker (nifedipine, NFD). We demonstrated that ghrelin significantly and reversibly decreases all three types of Ca2+ currents in GH3 cells through GHS receptors on the cell membrane and down-stream signaling systems. With different signal pathway inhibitors, we observed that ghrelin-induced reduction in voltage-gated Ca2+ currents in GH3 cells was mediated by a protein kinase G-dependent pathways. As ghrelin also stimulates Ca2+ release and prolongs the membrane depolarization, this reduction in voltage-gated Ca2+ currents may not be translated into a reduction in [Ca2+]i, or a decrease in GH secretion.
authors.affiliation: Department of Physiology, Fourth Military Medical University, Shannxi, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Han
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000737:chemistry / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000737:chemistry / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054439:Ghrelin / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D054440:Receptors, Ghrelin / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects; D059010:Single-Cell Analysis; D052683:Somatotrophs / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type; D054439:Ghrelin; D047428:Protein Kinase Inhibitors; D054440:Receptors, Ghrelin; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D006152:Cyclic GMP; D009543:Nifedipine