Journal of Clinical Endocrinology & Metabolism, Vol 72, 867-875, Copyright © 1991 by Endocrine Society

ARTICLES

Abnormal guanine nucleotide regulatory protein in MVP dysautonomia: evidence from reconstitution of Gs

AO Davies, CJ Su, A Balasubramanyam, J Codina and L Birnbaumer
Department of Internal Medicine, Baylor College of Medicine, Houston, Texas 77030.

We and others have used the term MVP dysautonomia for a particular subset of hyperadrenergic dysautonomia patients. The role of the stimulatory guanine nucleotide regulatory protein (Gs) in this dysautonomia was studied by cholate extraction of Gs from erythrocytes from 11 normal subjects and 14 symptomatic dysautonomic patients and reconstitution into cyc-S49 lymphoma membranes, which have normal receptor and adenylyl cyclase but lack Gs. Isoproterenol-stimulated adenylyl cyclase activity in the dysautonomia group was increased compared to that in controls [3.66 +/- 0.20 (mean +/- SE; n = 14) vs. 2.87 +/- 0.14 (n = 11) U cyc- reconstituted activity/mg erythrocyte protein; P less than 0.05]. beta-Adrenergic receptor high affinity state formation was greatest in the severely symptomatic group [KL/KH: severe symptoms, 130 +/- 48 (n = 6); mild symptoms, 33 +/- 7 (n = 7); control, 27 +/- 6 (n = 11); severe dysautonomia distinct, P less than 0.017]. Sodium dodecyl sulfate-polyacrylamide gels of cholera toxin- dependent ADP-ribosylated G-proteins yielded no gross distinction between severely symptomatic and control groups. This subset of hyperadrenergic dysautonomia patients, thus, has supercoupled beta 2- adrenergic receptors (increase in both agonist binding and cyclase activation) conferred by an abnormal Gs, whose effects on agonist binding reflect the severity of illness.

This article has been cited by other articles:

				R. E. Shapiro, B. Winters, M. Hales, T. Barnett, D. A. Schwinn, N. Flavahan, and D. E. Berkowitz Endogenous Circulating Sympatholytic Factor in Orthostatic Intolerance Hypertension, October 1, 2000; 36(4): 553 - 560. [Abstract] [Full Text] [PDF]

				D. H. C. Khoo, J. Parma, C. Rajasoorya, S. C. Ho, and G. Vassart A Germline Mutation of the Thyrotropin Receptor Gene Associated with Thyrotoxicosis and Mitral Valve Prolapse in a Chinese Family J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1459 - 1462. [Abstract] [Full Text]

				X. Yang, F. Y. G. Lee Sr., and G. S. Wand Increased Expression Of Gs{alpha} Enhances Activation Of The Adenylyl Cyclase Signal Transduction Cascade Mol. Endocrinol., July 1, 1997; 11(8): 1053 - 1061. [Abstract] [Full Text]