The secretion of growth hormone (GH) is inhibited by hypothalamic somatostatin (SRIF) in somatotropes through five subtypes of the somatostatin receptor (SSTRs1-5). We aimed to characterize the subtype(s) of SSTRs involved in the Ca(2+) current reduction in GH3 somatotrope cells using specific SSTR subtype agonists. Nystatin-perforated patch clamp was used to record voltage-gated Ca(2+) currents using a holding potential of -80mV in the presence of K(+) and Na(+) channel blockers. We first established the presence of T, L, N, and P/Q type Ca(2+) currents in GH3 cells using a variety of channel blockers (Ni(+), nifedipine, u-conotoxin GVIA, and u-agatoxin IVA). SRIF (200nM) 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 Ca(2+) currents to find the maximal effective concentration. Activation of SSTR2 with 10(-7)M and 10(-8)M L-797,976 decreased the voltage-gated Ca(2+) current and abolished any further decrease by SRIF. SSTR1, SSTR3, SSTR4, and SSTR5 agonists at 10(-7)M did not modify the voltage-gated Ca(2+) current and did not affect the Ca(2+) current response to SRIF. These results indicate that SSTR2 is mainly involved in regulating voltage-gated Ca(2+) currents by SRIF, which contributes to the decrease in [Ca(2+)]i and GH secretion by SRIF. Key words: somatostatin receptor subtypes, somatostatin receptors agonist, somatotrope.
|Pages (from-to)||E1863 - E1870|
|Number of pages||8|
|Journal||American Journal of Physiology - Endocrinology and Metabolism|
|Publication status||Published - 2007|