Correlation between agonist potency, desensitization and internalization of beta adrenergic receptors in a muscle cell line.
The mechanism(s) of agonist-induced desensitization of the beta adrenergic receptor-coupled adenylate cyclase has been investigated in the L8 skeletal muscle cell line. Different beta agonists stimulate cAMP accumulation in intact L8 cells with the following potency: Isoproterenol greater than Procaterol = Epinephrine greater than Norepinephrine greater than Phenylephrine. Preincubation of intact cells for 30 min at 37 degrees C with the same agonists induces a dose-dependent desensitization of beta receptor function. The degree of desensitization induced is correlated with the potency of agonists in stimulating cAMP accumulation. The same agonists induced internalization of the adrenergic beta receptor, with potency similar to that inducing desensitization and cAMP accumulation. Thus it is possible to conclude that in L8 cells beta receptor are of the beta 2 subtype and that agonist-induced beta adrenergic receptor desensitization proceeds via internalization of the beta adrenergic recognition site.
Sher
E
E
Clementi
F
F
D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009132:Muscles / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D000242:Cyclic AMP; D007545:Isoproterenol; D004837:Epinephrine; D010646:Phentolamine