title: Catecholamine-induced heterologous desensitization of rabbit luteal adenylyl cyclase: loss of luteinizing hormone responsiveness is associated with impaired G-protein function.
abstract: The effects of injecting epinephrine into pseudopregnant rabbits on the luteal adenylyl cyclase system were analyzed. Epinephrine-induced desensitization was heterologous and associated with a reduced response to isoproterenol, LH, NaF, and forskolin. Epinephrine-induced desensitization was rapid in onset, with a maximum decrease in responsiveness 6 h after treatment and responsiveness returning to control levels within 24 h of treatment. The changes in beta-adrenergic receptor content paralleled changes in catecholamine responsiveness. The affinity of the beta-receptors from treated animals decreased 1.5- to 2-fold before down-regulation. LH receptor number was not altered by epinephrine treatment, although responsiveness to LH was depressed. LH receptor affinity, however, was reduced about 2-fold by epinephrine treatment. Epinephrine treatment also altered G-protein function in corpora lutea, as assessed by reconstitution of adenylyl cyclase activity in S49 cyc- membranes and ADP ribosylation by cholera and pertussis toxins. NaF- and isoproterenol-reconstituting activities of luteal Gs (the stimulatory G-protein of adenylyl cyclase) were depressed for the first 6 h after treatment. The ability of cholera toxin to ADP ribosylate alpha s 46 and alpha s 45 was reduced 1.5-6 h and 3-12 h, respectively, after epinephrine treatment. The reduced ability of cholera toxin to ADP ribosylate alpha s 45 was associated with the decrease in LH receptor affinity after treatment. This supports the contention that alpha s 45 preferentially interacts with the LH receptor. These studies demonstrate that the loss of LH responsiveness upon epinephrine-induced heterologous desensitization is associated with altered G-protein function.
authors.affiliation: Department of Zoology, Iowa State University of Science and Technology, Ames 50011-3223.
authors.forename: B P
authors.initials: BP
authors.lastname: Jena
authors.forename: J
authors.initials: J
authors.lastname: Abramowitz
mesh_terms: D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002772:Cholera Toxin; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism / Q000502:physiology*; D037342:Pertussis Toxin; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000378:metabolism; D011974:Receptors, LH / Q000032:analysis / Q000378:metabolism; D010566:Virulence Factors, Bordetella
chemical_list: D037361:Adenylate Cyclase Toxin; D006063:Chorionic Gonadotropin; D011943:Receptors, Adrenergic, beta; D011974:Receptors, LH; D010566:Virulence Factors, Bordetella; D007986:Luteinizing Hormone; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D004837:Epinephrine