Effect of carbachol in the absence and presence of phenylephrine on Rb+ efflux and tension in rabbit left atria.
The muscarinic agonist carbachol produced a concentration-dependent increase in 86Rb+ efflux and decrease in tension in isolated, electrically stimulated rabbit left atria. However, the lowest concentration of carbachol tested produced only a very small increase in 86Rb+ efflux, while it caused a relatively greater decrease in tension. 4-Aminopyridine and pertussis toxin attenuated the carbachol-stimulated 86Rb+ efflux and negative inotropic effect. However, 4-aminopyridine had a greater inhibitory effect on carbachol-stimulated 86Rb+ efflux than on carbachol-induced decreases in tension. Pre-treatment of rabbits with pertussis toxin completely abolished the increase in 86Rb+ efflux and decrease in tension produced by carbachol in the presence of the alpha-adrenoceptor agonist phenylephrine. 4-Aminopyridine attenuated the negative inotropic response to carbachol in the presence of phenylephrine, but had less effect on the carbachol-induced increase in 86Rb+ efflux under these conditions. These results suggest that carbachol-induced increases in K+ efflux may contribute at least in part to the negative inotropic responses to carbachol in the presence and absence of phenylephrine. However, this may not be sufficient to explain the direct negative inotropic response of left atria to carbachol.
Ray
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Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
MacLeod
K M
KM
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006325:Heart Atria; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D012414:Rubidium Radioisotopes; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D010566:Virulence Factors, Bordetella; D010656:Phenylephrine; D002217:Carbachol; D015761:4-Aminopyridine; D037342:Pertussis Toxin