Abstract
Many hormones interact with receptors which stimulate the enzyme adenylate cyclase. Less well characterized are those receptors which mediate an inhibition of adenylate cyclase activity1. However, guanine nucleotides are clearly important in the regulation of both stimulatory and inhibitory receptors2. Monovalent cations, notably Na+, regulate many inhibitory receptor systems but apparently not stimulatory receptors1. We investigate here the effects of Na+ and guanine nucleotides on the adenylate cyclase-coupled inhibitory α2-adrenergic receptor of the rabbit platelet3. Computer modelling of adrenaline competition curves with 3H-dihydroergocryptine (3H-DHE) indicates that adrenaline induces two distinct affinity states of the α2 receptor—one of higher (α2H) and the other of lower (α2L) affinity. Guanyl-5′-yl-imidodiphosphate (Gpp(NH)p) seems to reduce adrenaline affinity by converting the high-affinity state into the low-affinity form of the receptor. In contrast, Na+ reduces adrenaline affinity at both the high- and low-affinity states of the α2 receptor while preserving receptor heterogeneity. Thus, guanine nucleotides and Na+ differ in the manner by which each reduces agonist affinity for the α2-adrenergic receptor.
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Howard Hughes Medical Institute Laboratory, Departments of Medicine (Cardiology) and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710
- Thomas Michel
- , Brian B. Hoffman
- & Robert J. Lefkowitz
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