Mechanism of desensitization of adenylate cyclase in lutropin. GTP-dependent uncoupling of the receptor.
Lutropin-sensitive adenylate cyclase ((EC 4.6.1.1) ATP pyrophosphate-lyase (cyclizing)) in purified rat ovarian plasma membranes is stimulated by lutropin 2- to 3-fold in the absence, but 15- to 20-fold in the presence of GTP or p(NH)ppG. Following 10 to 15 min of incubation at 30 degrees C in the presence of lutropin, enzyme activity declined (50%) in the presence of GTP but not in the presence of p(NH)ppG. This desensitizing process induced by lutropin and GTP is not seen if NaF is also included in the incubation medium. The desensitized state of the enzyme persists at 4 degrees C in membranes washed free of the incubation medium. In this state the enzyme is characterized by: (i) a reduced response to lutropin even in the presence of p(NH)ppG; (ii) its response to NaF is not different from that of untreated enzyme; (iii) it reconverts to a fully responsive state following incubation (10 min, 30 degrees C) in GTP-free medium, a process accelerated by p(NH)ppG; (iv) the receptor content as well as the stability of the receptor.hormone complex does not differ from that of untreated fully responsive enzyme. It is proposed that desensitization results from a GTP-dependent, hormone-stimulated reaction that leads to impaired coupling of the enzyme system. The desensitized state induced is transient and may revert to a responsive one under specified conditions.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004355:Drug Stability; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism / Q000494:pharmacology*; D010053:Ovary / Q000201:enzymology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*
D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D007986:Luteinizing Hormone; D000262:Adenylyl Cyclases; D005459:Fluorides