Discrimination between intact cell desensitization and agonist affinity changes.
The relationship between epinephrine-induced receptor-epinephrine affinity changes and intact cell adenylate cyclase activity was investigated using S49 lymphoma cells. It was demonstrated that 20 nM epinephrine caused desensitization (defined as a reduction in the rate of cAMP synthesis with time), but no significant change in receptor-epinephrine affinity as measured by competition with [125I]iodopindolol. On the other hand, treatment with 5 microM epinephrine caused no desensitization (as defined above), but did cause a very significant reduction in receptor-epinephrine affinity. It is suggested that there is a desensitization process which is distinct from the agonist affinity shift and which is expressed primarily as a change in the EC50 of the hormone-induced activation. The demonstration of extensive desensitization at low concentrations of hormone may have important physiological implications.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D004837:Epinephrine / Q000494:pharmacology; D007700:Kinetics; D008223:Lymphoma / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; C029247:3-iodopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D004837:Epinephrine