Acetylcholine Tachyphylaxis in Isolated Rabbit Atrium and Its Relation to Norepinephrine Stores

• Published in: Journal of pharmaceutical sciences 1970-09, Vol.59 (9), p.1252-1255
• Main Authors: David MacFarlane, M., Koppanyi, Theodore
• Format: Article
• Language: English
• Subjects: Acetylcholine - antagonists & inhibitors; Acetylcholine - pharmacology; Acetylcholine tachyphylaxis-isolated atrium; Acetylcholine tachyphylaxis—isolated atrium, rabbit; Animals; Atropine - pharmacology; Atropine effect-acetylcholine tachyphylaxis; Epinephrine - pharmacology; Heart Atria - drug effects; Male; Muscle Contraction - drug effects; Muscles - drug effects; Norepinephrine - metabolism; Norepinephrine - pharmacology; Norepinephrine stores; Norepinephrine stores, relationship—acetylcholine tachyphylaxis; rabbit; Rabbits; relationship-acetylcholine tachyphylaxis; Reserpine - pharmacology; Reserpine effect-acetylcholine; Reserpine effect—acetylcholine, tyramine activity; Tachyphylaxis - drug effects; Time Factors; Tyramine - pharmacology; tyramine activity
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600590907

Large concentrations of acetylcholine, in the presence of atropine, are known to produce positive inotropic and chronotropic responses in isolated, spontaneously beating rabbit atria. This response is due to release of norepinephrine from atrial tissue. After repeated concentrations of acetylcholine (100 mcg./kg.), in the presence of atropine (3 mcg./kg.), were added to the bath fluid at 10-min. intervals, the usual stimulatory responses to acetylcholine were not detected; i.e., the tissue was tachyphylactic to the actions of acetylcholine. If acetylcholine, in the presence of atropine, was given at intervals of more than 20 min., tachyphylaxis could not be observed. To investigate a possible link between acetylcholine tachyphylaxis and a decrease in the amount of norepinephrine available for release by acetylcholine, the atria were exposed to norepinephrine after acetylcholine tachyphylaxis was produced. Norepinephrine was allowed to remain in contact with tachyphylactic atrial tissues for 5 min. before being washed out. Acetylcholine now elicited its usual stimulatory effect. Epinephrine was also capable of restoring the response of tachyphylactic atria to acetylcholine. Atria excised from rabbits that were pretreated with reserpine did not respond to either acetylcholine or tyramine. When these preparations were incubated with norepinephrine, there was no return of the stimulatory response to acetylcholine, although the response to tyramine was restored.