Somatostatin decreases voltage-gated Ca2+ currents in GH3 cells through activation of somatostatin receptor 2.
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.
Yang
Seung-Kwon
SK
Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia.
Parkington
Helena C
HC
Epelbaum
Jacques
J
Keating
Damien J
DJ
Chen
Chen
C
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*
D000577:Amides; D015220:Calcium Channels; D007211:Indoles; C121854:L 779976; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2