Functional studies in atrium overexpressing A 1 ‐adenosine receptors

Adenosine and the A 1 ‐adenosine receptor agonist R‐PIA, exerted a negative inotropic effect in isolated, electrically driven left atria of wild‐type mice. In left atria of mice overexpressing the A 1 ‐adenosine receptor, adenosine and R‐PIA exerted a positive inotropic effect. The positive inotropic effect of adenosine and R‐PIA in transgenic atria could be blocked by the A 1 ‐adenosine receptor antagonist DPCPX. In the presence of isoprenaline, adenosine exerted a negative inotropic effect in wild‐type atria but a positive inotropic effect in atria from A 1 ‐adenosine receptor overexpressing mice. The rate of beating in right atria was lower in mice overexpressing A 1 ‐adenosine receptors compared with wild‐type. Adenosine exerted comparable negative chronotropic effects in right atria from both A 1 ‐adenosine receptor overexpressing and wild‐type mice. A 1 ‐adenosine receptor overexpression in the mouse heart can reverse the inotropic but not the chronotropic effects of adenosine, implying different receptor‐effector coupling mechanisms.British Journal of Pharmacology (1999) 128 , 1623–1629; doi: 10.1038/sj.bjp.0702963