title: Withdrawal of somatostatin augments L-type Ca2+ current in primary cultured rat somatotrophs.
abstract: It is known that withdrawal of somatostatin (SRIF) augments the growth hormone (GH) releasing hormone (GRF)-induced GH secretion. To investigate the mechanism of this augmentation in GH secretion, effects of GRF and SRIF on L-type Ca2+ current (Ba2+ was used as a charge carrier) or primary cultured rat somatotroph were studied by perforated patch clamp technique. The reason is that GRF-induced GH secretion is thought to be causally related to the influx of Ca2+ through L-type Ca2+ channels. 10 mM GRF augmented maximum amplitude of L-type Ba2+ current by 12.2% (n = 12). Subsequent application of SRIF slightly suppressed the currents but the suppression never exceeded the control level of the current. Removal of SRIF, however, promptly augmented the L-type Ba2+ current by 26.8%. Such off-response of SRIF was not observed in cells treated overnight with 100 ng/ml pertussis toxin. Further, specific inhibitor of protein kinase A, H-89 at 1 microM reversibly suppressed the augmentation of L-type Ba2+ current to control level. At 10 microM, H-89 suppressed L-type Ba2+ current by more than 40% from control level. These results suggest that (1) L-type Ca2+ channel of somatotroph is probably phosphorylated in a basal condition and may be slightly modulated by GRF through increased level of cAMP; (2) SRIF only slightly suppress the channel activity; (3) Withdrawal of SRIF facilitates the activity of L-type Ca2+ channel via PTX-sensitive G-protein, although the precise mechanism of this facilitation is unknown. The augmentation by SRIF-pretreatment of GRF-induced GH secretion may be at least partly due to the facilitation of the activity of L-type Ca2+ channel.
authors: Department of Physiology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors: M
authors: M
authors: Kato
mesh_terms: D000818:Animals; D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000494:pharmacology*; D013449:Sulfonamides
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D001464:Barium; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide