ABNORMAL GUANINE-NUCLEOTIDE REGULATORY PROTEIN IN MVP DYSAUTONOMIA - EVIDENCE FROM RECONSTITUTION OF GS

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]. beta-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 beta-2-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.