Decreased adenylate cyclase activity and expression of G(sα) in human myocardium after orthotopic cardiac transplantation

TY - JOUR

T1 - Decreased adenylate cyclase activity and expression of G(sα) in human myocardium after orthotopic cardiac transplantation

AU - Loh, E.

AU - Barnett, J. V.

AU - Feldman, A. M.

AU - Couper, G. S.

AU - Vatner, D. E.

AU - Colucci, W. S.

AU - Galper, J. B.

PY - 1995

Y1 - 1995

N2 - 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), GTPγS- 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(sα) protein was decreased by 61 ± 12% (n=8; P<.001). There was no change in the level of G(iα) 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(sα) mRNA was observed. There was no change in the level of mRNA for G(i-3α). Thus, after orthotopic cardiac transplantation in humans, guanine nucleotide-stimulated adenylate cyclase activity is decreased in parallel with decreased levels of G(sα) protein and mRNA.

AB - 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), GTPγS- 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(sα) protein was decreased by 61 ± 12% (n=8; P<.001). There was no change in the level of G(iα) 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(sα) mRNA was observed. There was no change in the level of mRNA for G(i-3α). Thus, after orthotopic cardiac transplantation in humans, guanine nucleotide-stimulated adenylate cyclase activity is decreased in parallel with decreased levels of G(sα) protein and mRNA.

KW - adenylate cyclase

KW - cardiac transplantation

KW - guanine nucleotide regulatory proteins

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U2 - https://doi.org/10.1161/01.RES.76.5.852

DO - https://doi.org/10.1161/01.RES.76.5.852

M3 - Article

C2 - 7729002

SN - 0009-7330

VL - 76

SP - 852

EP - 860

JO - Circulation Research

JF - Circulation Research

IS - 5

ER -