Interactions of beta-adrenergic receptors with a membrane protein other than the stimulatory guanine nucleotide-binding protein.
Beta-adrenergic receptors on membranes prepared from rat lung, wild-type S49 lymphoma cells, and the adenylate cyclase-deficient variant of S49 lymphoma cells (cyc-) bind the agonist [3H]hydroxybenzylisoproterenol ([3H]HBI) with high affinity and this binding of [3H]HBI can be inhibited by GTP. Membranes prepared from these tissues were incubated with the agonist [3H]HBI or the antagonist [125I]iodopindolol ([125I]IPIN), labeled receptors were solubilized with digitonin, and the apparent molecular sizes of the ligand-bound receptor complexes were determined by high-performance size-exclusion chromatography. Results with all three tissues demonstrated that receptors labeled with [125I]IPIN were retained by the size-exclusion columns longer than receptors labeled with [3H]HBI. Thus, the apparent molecular size of soluble beta-adrenergic receptors from rat lung, wild-type S49 cells, and cyc- S49 cells was larger when receptors were occupied with an agonist rather than an antagonist. The results suggest that receptors, including those on cyc- S49 cells, interact with a membrane protein, presumably a guanine nucleotide-binding protein. Since cyc- S49 cells do not contain a functional stimulatory guanine nucleotide-binding protein, but do contain a functional inhibitory guanine nucleotide-binding protein, an interaction between beta-adrenergic receptors and the inhibitory guanine nucleotide-binding protein may be responsible for the apparent increase in the molecular size of the receptor after occupation of the receptor with an agonist.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism; D007545:Isoproterenol / Q000031:analogs & derivatives / Q000378:metabolism; D008223:Lymphoma; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011943:Receptors, Adrenergic, beta; C015272:hydroxybenzylisoproterenol; C029247:3-iodopindolol; D010869:Pindolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol