title: Somatostatin decreases voltage-gated Ca2+ currents in GH3 cells through activation of somatostatin receptor 2.
abstract: The secretion of growth hormone (GH) is inhibited by hypothalamic somatostatin (SRIF) in somatotropes through five subtypes of the somatostatin receptor (SSTR1-SSTR5). We aimed to characterize the subtype(s) of SSTRs involved in the Ca2+ current reduction in GH3 somatotrope cells using specific SSTR subtype agonists. We used nystatin-perforated patch clamp to record voltage-gated Ca2+ currents, using a holding potential of -80 mV in the presence of K+ and Na+ channel blockers. We first established the presence of T-, L-, N-, and P/Q-type Ca2+ currents in GH3 cells using a variety of channel blockers (Ni+, nifedipine, omega-conotoxin GVIA, and omega-agatoxin IVA). SRIF (200 nM) reduced L- and N-type but not T- or P/Q-type currents in GH3 cells. A range of concentrations of each specific SSTR agonist was tested on Ca2+ currents to find the maximal effective concentration. Activation of SSTR2 with 10(-7) and 10(-8) M L-797,976 decreased the voltage-gated Ca2+ current and abolished any further decrease by SRIF. SSTR1, SSTR3, SSTR4, and SSTR5 agonists at 10(-7) M did not modify the voltage-gated Ca2+ current and did not affect the Ca2+ current response to SRIF. These results indicate that SSTR2 is involved mainly in regulating voltage-gated Ca2+ currents by SRIF, which contributes to the decrease in intracellular Ca2+ concentration and GH secretion by SRIF.
authors.affiliation: Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia.
authors.forename: Seung-Kwon
authors.initials: SK
authors.lastname: Yang
authors.forename: Helena C
authors.initials: HC
authors.lastname: Parkington
authors.forename: Jacques
authors.initials: J
authors.lastname: Epelbaum
authors.forename: Damien J
authors.initials: DJ
authors.lastname: Keating
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D007211:Indoles / Q000494:pharmacology; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D051381:Rats; D017481:Receptors, Somatostatin / Q000819:agonists / Q000187:drug effects* / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology*; D052683:Somatotrophs / Q000378:metabolism*
chemical_list: D000577:Amides; D015220:Calcium Channels; D007211:Indoles; C121854:L 779976; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2