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Science 5 March 1993:
Vol. 259. no. 5100, pp. 1453 - 1457
DOI: 10.1126/science.8383880
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Articles

Science, Vol 259, Issue 5100, 1453-1457
Copyright © 1993 by American Association for the Advancement of Science

articles

Antagonism of catecholamine receptor signaling by expression of cytoplasmic domains of the receptors

LM Luttrell, J Ostrowski, S Cotecchia, H Kendall, and RJ Lefkowitz

Department of Medicine, Duke University Medical Center, Durham, NC 27710.

The actions of many hormones and neurotransmitters are mediated by the members of a superfamily of receptors coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins). These receptors are characterized by a highly conserved topographical arrangement in which seven transmembrane domains are connected by intracellular and extracellular loops. The interaction between these receptors and G proteins is mediated in large part by the third intracellular loop of the receptor. Coexpression of the third intracellular loop of the alpha 1B-adrenergic receptor with its parent receptor inhibited receptor-mediated activation of phospholipase C. The inhibition extended to the closely related alpha 1C-adrenergic receptor subtype, but not the phospholipase C-coupled M1 muscarinic acetylcholine receptor nor the adenylate cyclase-coupled D1A dopamine receptor. These results suggest that the receptor-G protein interface may represent a target for receptor antagonist drugs.


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