AJP - Endocrinology and Metabolism, Vol 268, Issue 1 E40-E47, Copyright © 1995 by American Physiological Society
Functional characterization of somatostatin receptors expressed on hamster glucagonoma cells
H. C. Fehmann, M. Strowski and B. Goke
Department of Medicine, Philipps-University of Marburg, Germany.
We characterized somatostatin receptors expressed in hamster glucagonoma
INR1G9 cells and the effects of somatostatin on glucagon secretion,
proglucagon gene expression, and the adenosine 3',5'-cyclic monophosphate
(cAMP)-dependent signal-transduction cascade. 125I-labeled somatostatin was
displaced by somatostatin-14 and somatostatin-28 with a dissociation
constant of 2 nmol/l. Stable GTP analogues decreased binding of
125I-somatostatin to its receptors, suggesting an interaction of
somatostatin receptors with G proteins. Chemical cross-linking of
125I-somatostatin to its receptor revealed a molecular mass of the
ligand-receptor complex of 47 kDa. Somatostatin inhibited
forskolin-stimulated activation of adenylate cyclase [2.5 microM forskolin
(161%) + 1 microM somatostatin (128%); P < 0.05] and protein kinase A
[10 microM forskolin (143%) + 1 microM somatostatin (114%); P < 0.05]
but did not influence basal activities of these enzymes. Forskolin-induced
stimulation of cAMP generation was reduced by somatostatin [2.5 microM
forskolin (306%) + 1 microM somatostatin (145%); P < 0.05]. Somatostatin
inhibited forskolin, theophylline, and arginine stimulation of glucagon
secretion. Basal as well as forskolin-, theophylline-, and isobutyl
methylxanthine-induced proglucagon gene expression was significantly
reduced by somatostatin. Our data show that, in INR1G9 cells, somatostatin
receptors are at least in part coupled to the adenylate cyclase system.
Somatostatin is a potent negative regulator of both basal and
forskolin-stimulated proglucagon gene expression. The interaction with
forskolin occurs at the level of adenylate cyclase. The effect of
somatostatin on basal proglucagon gene transcription is most probably
mediated by an unrelated second messenger system. Somatostatin may
influence several functions of the pancreatic A cell.
