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(Circulation Research. 1995;76:852-860.)
© 1995 American Heart Association, Inc.

Articles

Decreased Adenylate Cyclase Activity and Expression of G_s in Human Myocardium After Orthotopic Cardiac Transplantation

Evan Loh, Joey V. Barnett, Arthur M. Feldman, Gregory S. Couper, Dorothy E. Vatner, Wilson S. Colucci, Jonas B. Galper

From the Department of Medicine (Cardiovascular Division), Hospital of the University of Pennsylvania, Philadelphia (E.L.); Department of Medicine (Cardiovascular Division) and Cardiac Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (G.S.C., W.S.C., J.B.G.); Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn (J.V.B.); Division of Cardiology, University of Pittsburgh (Pa) (A.M.F.); and Children's Service, Massachusetts General Hospital, Boston (D.E.V.).

Correspondence to Evan Loh, MD, Cardiovascular Division, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia PA 19104.

Abstract We studied several aspects of guanine nucleotide–stimulated adenylate cyclase function in patients after orthotopic cardiac transplantation. In 28 patients, adenylate cyclase activity was measured in endomyocardial biopsy samples obtained just before and at monthly intervals after cardiac transplantation. In biopsies obtained 6 months after transplantation, basal adenylate cyclase activity was decreased by 67% (n=12; P<.05), GTPS-stimulated adenylate cyclase activity was decreased by 78% (n=12; P<.05), Mn⁺²+forskolin–stimulated adenylate cyclase activity was decreased by 80% (n=8; P<.05), and Mn⁺²-stimulated adenylate cyclase activity (a measure of activity of the catalytic subunit of adenylate cyclase) was decreased by 83% (n=8, P<.05). Western blot analysis demonstrated that 6 months after cardiac transplantation, the level of G_s protein was decreased by 61±12% (n=8; P<.001). There was no change in the level of G_i as assessed by pertussis toxin–catalyzed ADP-ribosylation (n=4; P=NS). With the use of the quantitative polymerase chain reaction, a 50±10% (n=6; P<.001) reduction in the steady-state level of G_s mRNA was observed. There was no change in the level of mRNA for G_i-3. Thus, after orthotopic cardiac transplantation in humans, guanine nucleotide–stimulated adenylate cyclase activity is decreased in parallel with decreased levels of G_s protein and mRNA.

Key Words: cardiac transplantation • adenylate cyclase • guanine nucleotide regulatory proteins

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