摘要：

G protein-coupled receptors are cell surface receptors that mediate the effects of extracellular signals in the endocrine/paracrine and sensory systems. Experimental evidence is accumulating, which suggest that these receptors form dimers or higher order oligomers. The functional relevance of G protein-coupled receptor dimerization or oligomerization has been raised in a number of different processes, including ontogeny, internalization, ligand-induced regulation, pharmacological diversity and signal transduction of these receptors. Agonist-independent homo- and hetero-oligomerization of the angiotensin AT 1 receptor has been reported, and it has been suggested that hetero-oligomerization with β-adrenergic receptors leads to cross-inhibition of these receptors. Much less is known about the functional interactions between AT 1 receptor homo-oligomers. The aim of the present study was to analyze the functional interactions between these homo-oligomers by determining the functions of normal, AT 1 receptor blocker (candesartan) resistant (S109Y) and G protein coupling deficient (DRY/AAY) AT 1 receptors (co-)expressed in COS-7 cells. Although we have found no evidence that stimulation of a G protein coupling deficient receptor could cross-activate co-expressed normal receptors, candesartan binding to a signaling deficient receptor caused cross-inhibition of co-expressed candesartan resistant AT 1 receptors. Since the studied mutations were in the third intracellular helix of the receptor, the observed effects cannot be explained with domain swapping. These data suggest that AT 1 receptor blockers cause cross-inhibition of homo-oligomerized AT 1 receptors, and support the concept that receptor dimers/oligomers serve as the functional unit of G protein-coupled receptors.

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