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Journal of Clinical Endocrinology & Metabolism Vol. 72, No. 4 867-875
doi:10.1210/jcem-72-4-867
Copyright © 1991 by the Endocrine Society.
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Abnormal Guanine Nucleotide Regulatory Protein in MVP Dysautonomia: Evidence from Reconstitution of Gs*

ALBERT O. DAVIES, CHENG JIAN SU, ASHOK BALASUBRAMANYAM, JUAN CODINA and LUTZ BIRNBAUMER

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 (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 cycS49 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 < 0.05]. β-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 < 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 Gs, 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.




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