Hypothyroidism modulates beta adrenergic receptor adenylate cyclase interactions in rat reticulocytes.
We have investigated alterations in beta adrenergic receptor binding sites of rat reticulocytes occurring in animals rendered hypothyroid by thyroidectomy. Beta adrenergic receptor interactions were assessed by measuring the number of (-)[3H]-dihydroalprenolol binding sites and the ability of an agonist to compete for occupancy of the receptors. The number of receptors was significantly reduced in cells from the hypothyroid animals. In addition, there were significant agonist-specific alterations in binding. Using computer assisted curve fitting techniques, it was found that the ability of (-)isoproterenol to stabilize a high affinity guanine nucleotide sensitive "coupled" form of the receptor was impaired. Reticulocytes from hypothyroid animals have, in addition, a reduction in the concentration of the nucleotide regulatory protein as assessed by the number of 42,000 Mr substrates for cholera toxin catalyzed ADP ribosylation. These alterations are associated with reductions in catecholamine and NaF stimulated adenylate cyclase activity. Diminished coupling of beta adrenergic receptors with other regulatory components of the adenylate cyclase system represents a mechanism by which altered thyroid states modulate beta adrenergic receptor function and beta adrenergic responsiveness of tissues.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D004082:Dihydroalprenolol / Q000378:metabolism; D019204:GTP-Binding Proteins; D007037:Hypothyroidism / Q000378:metabolism*; D007545:Isoproterenol / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D012156:Reticulocytes / Q000378:metabolism*; D013965:Thyroidectomy
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011956:Receptors, Cell Surface; D004082:Dihydroalprenolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol