title: [Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on rat pancreatic acinar membranes].
abstract: To investigate whether somatostatin receptors couple to guanine nucleotide inhibitory protein, Ni, on rat pancreatic acinar membranes, the effects of guanine nucleotide analogs or pretreatment of acini with islet activating protein (IAP), pertussis toxin on labeled somatostatin binding were examined. Guanine nucleotides reduced labeled somatostatin binding to acinar membranes up to 80%, with rank order of potency being guanyl-5'-yl imidodiphosphate (Gpp(NH)p) greater than GTP greater than GDP greater than GMP. Scatchard analysis of the labeled somatostatin binding 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+ and Na+ also reduced labeled somatostatin binding. Furthermore, inhibitory effects of 100mM Na+ and Gpp(NH)p were additive in reducing labeled somatostatin binding. A half maximal inhibitory concentration of Gpp(NH)p was decreased to 10(-7)M in the presence of 100mM Na+ and 5mM Mg2+ as compared to 10(-6)M in the presence of 5mM Mg2+ alone. Results therefore suggest that Gpp(NH)p requires Mg2+ for Ni activation and Na+ increases sensitivity of Ni to guanine nucleotide analogs. When pancreatic acini were treated for 4 hours with varying concentrations of IAP, which has been shown to uncouple Ni-mediated communication between inhibitory receptors and adenylate cyclase catalytic unit, subsequent labeled somatostatin binding to the acinar membranes was decreased in a dose dependent manner. These results indicate that somatostatin receptors on pancreatic acinar membranes couple to guanine nucleotide inhibitory protein, Ni and thus somatostatin probably functions in the pancreas to regulate intracellular signal transduction via Ni.
authors.affiliation: Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Sakamoto
authors.forename: T
authors.initials: T
authors.lastname: Matozaki
authors.forename: M
authors.initials: M
authors.lastname: Nagao
authors.forename: H
authors.initials: H
authors.lastname: Nishisaki
authors.forename: S
authors.initials: S
authors.lastname: Baba
mesh_terms: D037361:Adenylate Cyclase Toxin; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000037:antagonists & inhibitors; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D006150:Guanine Nucleotides; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins