Altered activity of the inhibitory guanyl nucleotide-binding component (Ni) induced by pertussis toxin. Uncoupling of Ni from receptor with continued coupling of Ni to the catalytic unit.
The D-2 dopamine receptor mediates inhibition of adenylate cyclase in rat intermediate lobe; this receptor is linked to cyclase by the inhibitory guanyl nucleotide-binding protein (Ni). The functioning of components in the inhibitory system was compared in control and pertussis toxin-treated tissues. (-)-N-n-Propylnorapomorphine ((-)-NPA), a dopamine agonist, and 5'-guanylyl imidodiphosphate (Gpp(NH)p), a nonhydrolyzable GTP analog, caused a dose-dependent inhibition of adenylate cyclase in control tissue. Pertussis toxin abolished dopamine receptor-mediated inhibition of adenylate cyclase but did not alter Gpp(NH)p-induced inhibition of cyclase. In control tissue, GTP blocked Gpp(NH)p inhibition of cyclase in the absence, but not in the presence of (-)-NPA. Following pertussis toxin treatment, GTP blocked the inhibitory effect of Gpp(NH)p either in the absence or in the presence of (-)-NPA. Pertussis toxin did not alter the number of dopamine receptors or the affinity of the receptor for [3H]spiroperidol, a dopamine antagonist. However, pertussis toxin decreased the potency of (-)-NPA in the binding assay and abolished the ability of GTP to affect agonist binding. Furthermore, pertussis toxin abolished the dopamine receptor-mediated inhibition of immunoreactive alpha-melanocyte-stimulating hormone release, and induced the ADP-ribosylation of the Mr = 41,000 subunit of Ni.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D019204:GTP-Binding Proteins; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D037342:Pertussis Toxin; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism; D010566:Virulence Factors, Bordetella
D037361:Adenylate Cyclase Toxin; D001427:Bacterial Toxins; D011956:Receptors, Cell Surface; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D006165:Guanylyl Imidodiphosphate; D013134:Spiperone; D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases