Phenotypic changes of adrenomedullin receptor components, RAMP2, and CRLR mRNA expression in cultured rat vascular smooth muscle cells

Adrenomedullin is known to inhibit cell proliferation in cultured rat vascu lar smooth muscle cells, through a cAMP-dependent process. The calcitonin r eceptor-like receptor could function as an adrenomedullin receptor when co- expressed with receptor activity-modifying protein 2. To determine whether vascular adrenomedullin receptor components, the calcitonin receptor-like r eceptor and the receptor activity-modifying protein 2, phenotypically chang e during in vitro culture conditions, we examined the expression of adrenom edullin receptor components, adrenomedullin-induced cAMP production, and th e inhibition of cell proliferation in culture rat vascular smooth muscle ce lls during serial passages. The results demonstrated that the receptor acti vity-modifying protein 2 and calcitonin receptor-like receptor mRNAs increa sed in a passage-dependent manner in rat vascular smooth muscle cells. Furt hermore, the responses of both the elevation of cAMP and the inhibition of cell proliferation became larger in vascular smooth muscle cells with an in creasing number of passages. The results suggest that the increase in funct ional AM receptor during phenotypic change may in part contribute to the de velopment of vascular lesions, such as in atherosclerosis. (C) 2001 Academi c Press.