Activation of beta 2-adrenergic receptors on mouse anterior pituitary tumor cells increases cyclic adenosine 3':5'-monophosphate synthesis and adrenocorticotropin release.
AtT-20 cells comprise a mouse anterior pituitary tumor cell line that synthesizes and secretes adrenocorticotropin hormone (ACTH). beta-Adrenergic receptors were characterized on AtT-20 cells using receptor binding methodology and the ability of beta-receptor agonists to stimulate intracellular cyclic adenosine 3':5'-monophosphate (cAMP) formation and the release of ACTH immunoreactivity. The density of beta-receptors on membrane preparations of these cells is 64 fmol/mg of protein and their affinity constant (KD value) for tritiated dihydroalprenolol is 11 nM. The binding of [3H] dihydroalprenolol to AtT-20 cells is stereoselectively inhibited by propranolol and isoproterenol but is not affected by phentolamine. The beta-receptors on these cells appear to be of the beta 2-receptor subtype since a selective beta 2-receptor agonist, salmefamol, can inhibit [3H]dihydroalprenolol binding, whereas practolol, a beta 1-receptor blocker, is ineffective. (-)-Isoproterenol stimulates cAMP formation in AtT-20 cells and this effect is blocked by dl-propranolol. Both l-epinephrine and l-norepinephrine induce dose-dependent increases in cAMP formation with the former agonist being more potent. Salmefamol also stimulates cAMP formation in these cells. The secretion of ACTH from AtT-20 cells is induced by (-)-isoproterenol as well as by other adrenergic agonists. The isoproterenol effect on ACTH release is stereoselective, calcium dependent, and blocked by dl-propranolol but not by phentolamine or practolol.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D004082:Dihydroalprenolol / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009374:Neoplasms, Experimental / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000503:physiopathology*; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D000324:Adrenocorticotropic Hormone; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine