Inhibitory control of growth hormone secretion by somatostatin in rat pituitary GC cells: sst2 but not sst1 receptors are coupled to an inhibition of single-cell intracellular free calcium concentrations

Abstract

Rat pituitary tumor cells (GC cells) exhibit spontaneous oscillations of intracellular free calcium concentration ([Ca2+]i) that allow a continuous release of growth hormone (GH). Of the SRIH receptor subtypes (sst receptors) mediating SRIH action, sst1 and sst2 receptors are highly expressed by GC cell membranes. In the present study, the effects of sst1 or sst2 receptor activation on single-cell [Ca2+]i were investigated in GC cells by confocal fluorescence microscopy. In addition, the effects of sst1 or sst2 receptor activation on GH secretion were also studied. Our results demonstrate that SRIH decreases [Ca2+]i baseline and almost completely blocks Ca2+ transients through the activation of sst2 but not of sst1 receptors. In contrast, SRIH effectively inhibits GH secretion through the activation of both sst1 and sst2 receptors. Blocking Ca2+ transients is less efficient than SRIH to inhibit GH release. The cyclic octapeptide, CYN-154806, antagonizes sst2 receptors at [Ca2+]i since it abolishes the sst2 receptor-mediated inhibition of [Ca2+]i without affecting single-cell Ca2+ signals. Unexpectedly, CYN-154806 alone potently inhibits GH secretion through the involvement of pertussis toxin-sensitive G proteins. In conclusion, the present results demonstrate that SRIH inhibition of GH release in GC cells involves mechanisms either dependent or independent on SRIH modulation of [Ca2+]i. The implications of CYN-154806 inhibition of GH secretion are discussed.