Possible involvement of pertussis toxin substrates (Gi, Go) in desipramine-induced refractoriness of adenylate cyclase in cerebral cortices of rats.
To evaluate the efficiency of coupling between beta-receptor and adenylate cyclase catalyst via a GTP-binding protein, Gs, in the brain membrane two parameters were employed: a beta-agonist-induced increase in the membrane GTP-dependent adenylate cyclase activity and a beta-agonist-induced shortening of the lag time preceding the onset of the steady-state activation by guanyl-5'-yl-beta-gamma-imidodiphosphate [Gpp(NH)p] of the membrane cyclase. Both parameters showed lower values in membranes from desipramine-treated rats compared with untreated rats. Thus, coupling of beta-adrenergic receptors to adenylate cyclase in the brain membrane was impaired by the desipramine treatment. Rats once injected intraventricularly with islet-activating protein (IAP), pertussis toxin, were subjected to desipramine treatment, for the purpose of studying effects of another kind of the GTP-binding protein (Gi), which loses its function as a signal transducer on being ADP-ribosylated selectively by the toxin. IAP treatment did not impair the beta-receptor coupling by itself, since neither of the above two parameters for the coupling were reduced by IAP treatment. Moreover, the first parameter was normalized, though the second one was not, by superimposition of the IAP treatment upon the desipramine-treated rats. It seems likely, therefore, that Gi interacts with a Gs-adenylate cyclase coupling in an inhibitory fashion in brain membranes. The desensitization might be overcome when the inhibitory interaction of Gi on the subsequent process is attenuated by IAP treatment.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D003891:Desipramine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000378:metabolism* / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D003891:Desipramine