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

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 _α_2-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 _α_2 receptor—one of higher (_α_2H) and the other of lower (_α_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. In contrast, Na+ reduces adrenaline affinity at both the high- and low-affinity states of the _α_2 receptor while preserving receptor

heterogeneity. Thus, guanine nucleotides and Na+ differ in the manner by which each reduces agonist affinity for the _α_2-adrenergic receptor. Access through your institution Buy or

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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 Authors * Thomas Michel View author publications You can also search for this author inPubMed Google Scholar * Brian B. Hoffman View author publications You

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Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Michel, T., Hoffman, B. & Lefkowitz, R. Differential regulation of the _α_2-adrenergic receptor by Na+ and guanine

nucleotides. _Nature_ 288, 709–711 (1980). https://doi.org/10.1038/288709a0 Download citation * Received: 28 May 1980 * Accepted: 11 August 1980 * Issue Date: 18 December 1980 * DOI:

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