Differential regulation of the α2-adrenergic receptor by Na+ and guanine nucleotides

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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 activity. Guanine nucleotides are clearly important in the regulation of stimulatory and inhibitory receptors. Monovalent cations, notably Na+, regulate many inhibitory receptor systems but apparently not stimulatory receptors. The effects of Na+ and guanine nucleotides were studied on the adenylate cyclase-coupled inhibitory .alpha.2-adrenergic receptor of the rabbit platelet. Computer modeling of adrenaline [epinephrine] competition curves with 3H-dihydroergocryptine (3H-DHE) indicates that adrenaline induces 2 distinct affinity states of the .alpha.2 receptor, one of higher (.alpha.2H) and the other of lower (.alpha.2L) 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. Na+ reduces adrenaline affinity at the high- and low-affinity states of the .alpha.2 receptor while preserving receptor heterogeneity. Guanine nucleotides and Na+ differ in the manner by which each reduces agonist affinity for the .alpha.2-adrenergic receptor.

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