Inhibitory control of growth hormone secretion by somatostatin in rat pituitary GC cells: sst(2) but not sst(1) receptors are coupled to inhibition of single-cell intracellular free calcium concentrations.
Rat pituitary tumor cells (GC cells) exhibit spontaneous oscillations of intracellular free calcium concentration ([Ca(2+)](i)) that allow continuous release of growth hormone (GH). Of the somatostatin (SRIH) receptor subtypes (sst receptors) mediating SRIH action, sst(1) and sst(2) receptors are highly expressed by GC cell membranes. In the present study, the effects of sst(1) or sst(2) receptor activation on single-cell [Ca(2+)](i) were investigated in GC cells by confocal fluorescence microscopy. In addition, the effects of sst(1) or sst(2) receptor activation on GH secretion were also studied. Our results demonstrate that SRIH decreases [Ca(2+)](i) baseline and almost completely blocks Ca(2+) transients through activation of sst(2) but not of sst(1) receptors. In contrast, SRIH effectively inhibits GH secretion through activation of both sst(1) and sst(2) receptors. Blocking Ca(2+) transients is less efficient than SRIH to inhibit GH release. The cyclic octapeptide, CYN-154806, antagonizes sst(2) receptors at [Ca(2+)](i) since it abolishes the sst(2) receptor-mediated inhibition of [Ca(2+)](i) without affecting single-cell Ca(2+) signals. On the other hand, 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 [Ca(2+)](i). The implications of CYN-154806 inhibition of GH secretion are discussed.
Cervia
Davide
D
Department of Physiology and Biochemistry G. Moruzzi, University of Pisa, Italy.
Petrucci
Cristina
C
Bluet-Pajot
Marie Thérèse
MT
Epelbaum
Jacques
J
Bagnoli
Paola
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D013006:Growth Hormone / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology; D015282:Octreotide / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*
C110576:CH 275; C403089:CYN 154806; D006728:Hormones; D009842:Oligopeptides; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D013004:Somatostatin; D013006:Growth Hormone; C093733:somatostatin receptor 2; D015282:Octreotide; D002118:Calcium