Muscarinic receptor subtypes mediating negative chrono- and inotropic responses in isolated, blood-perfused dog right atria.
1. Negative chrono- and inotropic responses to both carbachol (CCh) into the sinus node artery and electrical stimulation of vagal nerve fibres (ES) were studied in the isolated, blood-perfused canine right atrium, using four muscarinic receptor antagonists, atropine, 4-DAMP, AF-DX 116 and pirenzepine. 2. ES and CCh evoked negative chrono- and inotropic responses in a frequency-dependent manner and in a dose-related manner, respectively. 3. Each antagonist inhibited these negative chrono- and inotropic responses in a dose-dependent manner. The ranking order of blocking potency (ID50) was atropine greater than or equal to 4-DAMP greater than AF-DX 116 greater than pirenzepine. 4. The ID50 of atropine, 4-DAMP or AF-DX 116 against sinus rate decreases induced by CCh or ES was not significantly different from that against the atrial tension decreases. In contrast, the ID50 of pirenzepine against sinus rate decreases evoked by CCh (17 nmol) or ES (20 nmol) was significantly smaller than that for the atrial tension decrease (CCh, 200 and ES, 53 nmol, respectively). 5. These results suggest that, in the isolated dog atrium, M2-receptor-mediated-responses are predominant. However, M1-receptor activation may also be involved in sinus rate response.
Akahane
K
K
Department of Pharmacology, Shinshu University School of Medicine, Mastumoto, Japan.
Furukawa
Y
Y
Karasawa
Y
Y
Chiba
S
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000037:antagonists & inhibitors*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014630:Vagus Nerve
D002316:Cardiotonic Agents; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol