AJP - Gastrointestinal and Liver Physiology, Vol 253, Issue 3 308-G314, Copyright © 1987 by American Physiological Society
Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes
C. Sakamoto, T. Matozaki, M. Nagao and S. Baba
Guanine nucleotides and pertussis toxin were used to investigate whether
somatostatin receptors interact with the guanine nucleotide inhibitory
protein (Ni) on pancreatic acinar membranes in the rat. Guanine nucleotides
reduced 125I-[Tyr1]somatostatin binding to acinar membranes up to 80%, with
rank order of potency being 5'-guanylyl imidodiphosphate [Gpp(NH)p] greater
than GTP greater than GDP greater than GMP. Scatchard analysis revealed
that the decrease in somatostatin binding caused by Gpp(NH)p was due to the
decrease in the maximum binding capacity without a significant change in
the binding affinity. The inhibitory effect of Gpp(NH)p was partially
abolished in the absence of Mg2+. When pancreatic acini were treated with 1
microgram/ml pertussis toxin for 4 h, subsequent 125I-[Tyr1]somatostatin
binding to acinar membranes was reduced. Gpp(NH)p further decreased
somatostatin binding to islet-activating protein (IAP)-treated acinar
membranes. Pertussis toxin treatment also abolished the inhibitory effect
of somatostatin on vasoactive intestinal peptide-stimulated increase in
cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the
acini. Furthermore, exposure of acini to IAP caused ADP ribosylation of a
membrane protein with Mr = 41,000 in parallel to the inhibition of cAMP
accumulation in acini. The present results suggest, therefore, that 1)
somatostatin probably functions in the pancreas to regulate adenylate
cyclase enzyme system via Ni, 2) the extent of modification of Ni is
correlated with the ability of somatostatin to inhibit cAMP accumulation in
acini, and 3) guanine nucleotides also inhibit somatostatin binding to its
receptor.
