PMID: 8967968Dec 1, 1996Paper

Inverse agonist-induced up-regulation of the human beta2-adrenoceptor in transfected neuroblastoma X glioma hybrid cells

Molecular Pharmacology
D J MacEwan, G Milligan

Abstract

Neuroblastoma X glioma hybrid NG108-15 cells were transfected to express stably either the wild-type human beta2-adrenoceptor or a constitutively active mutant (CAM) version of this receptor. Basal adenylyl cyclase activity in cells expressing the CAM beta2-adrenoceptor correlated well with the level of expression of the receptor and was substantially greater than that in cells expressing the wild-type beta2-adrenoceptor. The CAM beta2-adrenoceptor displayed higher affinity for the agonist isoprenaline than the wild-type receptor but not for the antagonist alprenolol or the inverse agonist betaxolol. Pretreatment of cells harboring the CAM beta2-adrenoceptor with betaxolol resulted in a large (4-7-fold within 24 hr) up-regulation in levels of this receptor. This was not observed after exposure of the CAM beta2-adrenoceptor-expressing cells to alprenolol, and a much smaller effect of betaxolol was produced in cells expressing the wild-type receptor. Betaxolol-mediated up-regulation of the CAM beta2-adrenoceptor was both time and concentration dependent. However, this up-regulation did not result in a substantial alteration in the cellular distribution profile of the receptor. Half-maximal up-regulation of the CAM beta2-adrenocep...Continue Reading

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