This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DAVIES, A. O. Articles by BIRNBAUMER, L. Search for Related Content PubMed PubMed Citation Articles by DAVIES, A. O. Articles by BIRNBAUMER, L.

Abnormal Guanine Nucleotide Regulatory Protein in MVP Dysautonomia: Evidence from Reconstitution of G_s^*

Pulmonary and Critical Care Medicine Section, Department of Internal Medicine (A.O.D.), the Section on Hypertension and Clinical Pharmacology, Department of Internal Medicine, and Center for Experimental Therapeutics (A.O.D., C.J.S., A.B.), the Department of Molecular Physiology and Biophysics (A.O.D., L.B.), and the Department of Cell Biology (J.C., L.B.), Baylor College of Medicine Houston, Texas 77030; and the Department of Medicine, Guangzou Medical College (C.J.S.) Guangzou, People's Republic of China

Address all correspondence and requests for requests to: Albert O. Davies, M.D., Department of Internal Medicine 520B, Baylor College of Medicine, One Baylor Plaza, 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 (G_s) in this dysautonomia was studied by cholate extraction of G_s 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 G_s. 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 < 0.05]. β-Adrenergic receptor high affinity state formation was greatest in the severely symptomatic group [K_L/K_H: severe symptoms, 130 ± 48 (n = 6); mild symptoms, 33 ± 7 (n = 7); control, 27 ± 6 (n = 11); severe dysautonomia distinct, P < 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 β₂-adrenergic receptors (increase in both agonist binding and cyclase activation) conferred by an abnormal G_s, whose effects on agonist binding reflect the severity of illness. (J Clin Endocrinol Metab 72: 867–875, 1991)

^* This work was supported in part by NIH Grants DK-35113 (to A.O.D.), DK-41780 (to A.O.D.), DK-19318 (to L.B.), HL-31164 (to L.B.), and HL-39262 (to L.B.) and the Baylor College of Medicine Diabetes and Endocrinology Research Center (DK-27685).

Received June 18, 1990.

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]