Pertussis toxin sensitive and insensitive effects of adenosine and carbachol in murine atria overexpressing A(1)-adenosine receptors.

Abstract

1 It was investigated how A(1)-adenosine receptor overexpression alters the effects of carbachol on force of contraction and beating rate in isolated murine atria. Moreover, the influence of pertussis toxin on the inotropic and chronotropic effects of adenosine and carbachol in A(1)-adenosine receptor overexpressing atria was studied. 2 Adenosine and carbachol alone exerted negative inotropic and chronotropic effects in electrically driven left atrium or spontaneously beating right atrium of wild-type mice. 3 These effects were abolished or reversed by pre-treatment of animals with pertussis toxin which can interfere with signal transduction through G-proteins. 4 Adenosine and carbachol exerted positive inotropic but negative chronotropic effects in atrium overexpressing A(1)-adenosine receptors from transgenic mice. 5 The positive inotropic effects of adenosine and carbachol were qualitatively unaltered whereas the negative chronotropic effects were abolished or reversed in atrium overexpressing A(1)-adenosine receptors after pre-treatment by pertussis toxin. 6 Qualitatively similar effects for adenosine and carbachol were noted in the presence of isoprenaline, beta-adrenoceptor agonist. 7 It is concluded that overexpression of A(1)-adenosine receptors also affects the signal transduction of other heptahelical, G-protein coupled receptors like the M-cholinoceptor in the heart. The chronotropic but not the inotropic effects of adenosine and carbachol in transgenic atrium were mediated via pertussis toxin sensitive G-proteins.