title: [Coupling of inhibitory GTP binding protein to somatostatin receptors on rat cerebrocortical membranes].
abstract: We studied the interaction between somatostatin receptors and inhibitory GTP binding protein in rat cerebrocortical membranes. Guanine nucleotides reduced [125I-Tyr1] somatostatin binding to cerebrocortical membranes in a dose-dependent manner with rank order of potency being guanyl-5'-yl-imidodiphosphate (Gpp(NH)p) greater than GTP greater than GMP. Maximum reduction of the binding to 32% of control was observed in the presence of 10(-5) M Gpp(NH)p. Scatchard analysis of the labeled somatostatin binding revealed that the decrease in the binding by Gpp(NH)p was due to the decrease in the binding affinity for somatostatin. Divalent cations, such as Mg++, Mn++, and Ca++, caused an increase in labeled somatostatin binding to membranes with the maximum binding observed at a concentration of 10, 10, 1 mM, respectively. However, Na+ decreased a labeled somatostatin binding in a dose-dependent manner, and half maximum inhibition of the binding was observed at 10 mM Na+. Moreover, Gpp(NH)p and Na+ lowered labeled somatostatin binding in an additive fashion. When cerebrocortical membranes were treated at 37 degrees C for 40 min with various concentrations of Islet-Activating-Protein (IAP), which had been preactivated with dithiothreitol, subsequent labeled somatostatin binding to the membranes was decreased in a dose-dependent manner. 30 micrograms/ml IAP treatment caused a decrease in the binding to 50% of control, which was characterized by the decreased binding affinity without a significant change in the binding capacity. Furthermore, exposure of IAP plus NAD to cerebrocortical membranes caused ADP-ribosylation of a membrane protein with Mr = 41,000 on autoradiogram. Such an IAP treatment of cerebrocortical membranes abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in adenylate cyclase activity. These results suggest that somatostatin receptors in the brain couple to inhibitory GTP binding protein, which mediates adenylate cyclase inhibition by somatostatin.
authors.affiliation: Second Department of Internal Medicine, Kobe University School of Medicine.
authors.forename: M
authors.initials: M
authors.lastname: Nagao
authors.forename: C
authors.initials: C
authors.lastname: Sakamoto
authors.forename: T
authors.initials: T
authors.lastname: Matozaki
authors.forename: H
authors.initials: H
authors.lastname: Nishizaki
authors.forename: Y
authors.initials: Y
authors.lastname: Konda
authors.forename: O
authors.initials: O
authors.lastname: Nakano
authors.forename: S
authors.initials: S
authors.lastname: Baba
mesh_terms: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism*; D003864:Depression, Chemical; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000494:pharmacology; D008297:Male; D037342:Pertussis Toxin; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017481:Receptors, Somatostatin; D012964:Sodium / Q000494:pharmacology; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D006150:Guanine Nucleotides; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D012964:Sodium; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins