Nonlinear relationship between alpha 1-adrenergic receptor occupancy and norepinephrine-stimulated calcium flux in cultured vascular smooth muscle cells

Journal Article · Wed May 01 00:00:00 EDT 1985 · Mol. Pharmacol.; (United States)

OSTI ID:5219586

Colucci, W S; Brock, T A; Gimbrone, Jr, M A; Alexander, R W

To determine the relationship between vascular alpha 1-adrenergic receptor occupancy and receptor-coupled calcium flux, the authors have studied (/sup 3/H)prazosin binding and l-norepinephrine-induced /sup 45/Ca efflux in cultured vascular smooth muscle cells isolated from the rabbit aorta. In a crude cellular homogenate, (/sup 3/H)prazosin bound to a single high affinity site, whereas l-norepinephrine (NE) binding was best described by a two-site model. NE-stimulated /sup 45/Ca efflux was concentration-dependent (EC/sup 50/ = 108 nM) and potently inhibited by prazosin (IC/sup 50/ = 0.15 nM). For the total receptor pool identified by (/sup 3/H)prazosin binding, the relationship between receptor occupancy by NE and NE-stimulated /sup 45/Ca efflux was markedly nonlinear, such that 50% of maximum NE-stimulated efflux occurred with occupancy of only approximately 7% of receptors. These two experimental approaches provide direct evidence for the presence in cultured rabbit aortic smooth muscle cells of a sizable pool of alpha 1-adrenergic receptors in excess of those needed for maximum NE-stimulated /sup 45/Ca efflux. This evidence of ''spare'' receptors, together with the finding of two affinity states of agonist binding, raises the possibility of functional heterogeneity of alpha 1-adrenergic receptors in this system.

• Research Organization: Brigham and Women's Hospital, Boston, MA
• OSTI ID: 5219586
• Journal Information: Mol. Pharmacol.; (United States), Vol. 5
• Country of Publication: United States
• Language: English

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