title: The in vitro regulation of growth hormone secretion by orexins.
abstract: Orexins, orexigenic neuropeptides, have recently been discovered in lateral hypothalamus and play an important role in the regulation of pituitary hormone secretion. Two subtypes of orexin receptors (orexin-1 and orexin-2) have been demonstrated in pituitaries. In this experiment, the effects of orexins on voltage-gated Ca2+ currents and the GH release in primary cultured ovine somatotropes were examined. Voltage-gated Ca2+ currents were isolated in ovine somatotropes as L, T, and N currents using whole-cell patch-clamp techniques and specific Ca2+ channel blocker and toxin. Application of orexin-A or orexin-B (100 nM) significantly, dose-dependently, and reversibly increased only nifedipine-sensitive L-type Ca2+ current. Inhibitors of PKC (calphostin C, PKC inhibitory peptide) but not inhibitors of PKA (H89, PKA inhibitory peptide) cancelled the increase in the L current by orexins. Co-administration of orexin-A and GHRH (10 nM) showed an additive effect on the L current. Specific intracellular Ca2+-store-depleting reagent, thapsigargin (1 microM), did not affect the orexin-induced increase in the L current. Orexin-B alone slightly increased GH release and co-administration of orexin-A and GHRH synergistically stimulated GH secretion in vitro. It is therefore suggested that orexins may play an important role in regulating GHRH-stimulated GH secretion through an increase in the L-type Ca2+ current and the PKC-mediated signaling pathways in ovine somatotropes.
authors: Prince Henry's Institute of Medical Research, and Department of Physiology, PO Box 5152, Monash University, Clayton, Victoria 3168, Australia. chen.chen@phimr.monash.edu.au
authors: Chen
authors: C
authors: Chen
authors: Ruwei
authors: R
authors: Xu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D015640:Ion Channel Gating / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D000068797:Orexins; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D015290:Second Messenger Systems / Q000502:physiology; D012756:Sheep; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002352:Carrier Proteins; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D020960:omega-Conotoxins; D019382:Human Growth Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D017868:Cyclic AMP-Dependent Protein Kinases; D009543:Nifedipine; D002118:Calcium