Pertussis toxin sensitive and insensitive effects of adenosine and carbachol in murine atria overexpressing A(1)-adenosine receptors.
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.
Neumann
Joachim
J
Institut für Pharmakologie und Toxikologie, Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Domagkstrasse 12, D-48129 Münster, Germany.
Boknik
Peter
P
Matherne
G Paul
GP
Lankford
Amy
A
Schmitz
Wilhelm
W
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D037342:Pertussis Toxin / Q000494:pharmacology*; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis* / Q000235:genetics
D018047:Receptors, Purinergic P1; D002217:Carbachol; D037342:Pertussis Toxin; D000241:Adenosine