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Up‐regulation of a constitutively active form of the β 2 ‐adrenoceptor by sustained treatment with inverse agonists but not antagonists
Author(s) -
MacEwan David J.,
Milligan Graeme
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(96)01300-2
Subject(s) - inverse agonist , adenylyl cyclase , propranolol , medicine , endocrinology , betaxolol , agonist , receptor , chemistry , antagonist , dihydroalprenolol , pharmacology , biology , partial agonist , timolol , neuroscience , glaucoma
In neuroblastoma × glioma hybrid, NG108‐15, cells transfected to stably express a constitutively active mutant (CAM) form of the human R2‐adrenoceptor, the β‐adrenoceptor ligands sotalol and betaxolol functioned as inverse agonists as they reduced basal adenylyl cyclase activity whereas the antagonists dihydroalprenolol and propranolol did not. Maintained presence of the CAM β 2 ‐adrenoceptor inverse agonists but not the antagonists in the culture medium of the cells resulted in a substantial, concentration‐dependent, up‐regulation of the CAM β 2 ‐adrenoceptor. Up‐regulation of the CAM β 2 ‐adrenoceptor by the inverse agonists was prevented by co‐incubation of the cells with either propranolol or dihydroalprenolol. Neither maintained elevation of cAMP levels nor the inhibition of adenylyl cyclase activity altered the ability of the inverse agonist ligands to cause receptor up‐regulation.