Functional studies in atrium overexpressing A1-adenosine receptors.
1. Adenosine and the A1-adenosine receptor agonist R-PIA, exerted a negative inotropic effect in isolated, electrically driven left atria of wild-type mice. 2. In left atria of mice overexpressing the A1-adenosine receptor, adenosine and R-PIA exerted a positive inotropic effect. 3. The positive inotropic effect of adenosine and R-PIA in transgenic atria could be blocked by the A1-adenosine receptor antagonist DPCPX. 4. In the presence of isoprenaline, adenosine exerted a negative inotropic effect in wild-type atria but a positive inotropic effect in atria from A1-adenosine receptor overexpressing mice. 5. The rate of beating in right atria was lower in mice overexpressing A1-adenosine receptors compared with wild-type. 6. Adenosine exerted comparable negative chronotropic effects in right atria from both A1-adenosine receptor overexpressing and wild-type mice. 7. A1-adenosine receptor overexpression in the mouse heart can reverse the inotropic but not the chronotropic effects of adenosine, implying different receptor-effector coupling mechanisms.
Neumann
J
J
Institut für Pharmakologie und Toxikologie, Universität Münster, D-48149 Münster, Germany.
Vahlensieck
U
U
Boknik
P
P
Linck
B
B
Lüss
H
H
Müller
F U
FU
Matherne
G P
GP
Schmitz
W
W
D000241:Adenosine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D016275:Atrial Function / Q000187:drug effects / Q000502:physiology*; D016279:Atrial Function, Left / Q000187:drug effects / Q000502:physiology; D016280:Atrial Function, Right / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis* / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011943:Receptors, Adrenergic, beta; D018047:Receptors, Purinergic P1; D000241:Adenosine