Muscarinic feedback inhibition of acetylcholine release from the myenteric plexus in the guinea pig ileum and its status after chronic exposure to morphine

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Abstract
Atropine (10−8–10−6 M) produced a dose-related increase in the release of ACh from the electrically stimulated longitudinal muscle – myenteric plexus preparation. This increase in release was frequency dependent, being greater at low frequencies of stimulation where the pulse release of ACh was greater than at high frequencies. The muscarinic agonist oxotremorine (up to 100 μM) did not inhibit ACh release although 100 μM oxotremorine did antagonize the ability of atropine to increase release. The effect of chronic exposure to morphine, both in vivo and in vitro, on the reactivity of muscarinic receptors mediating this increase was examined. Neither the control rate of ACh release nor the dose–response curve for atropine were altered by (a) an 8-day morphine injection schedule, and (b) exposure of the tissue to morphine in the bath for 90 min. The results of this study support the existence of a muscarinic feedback mechanism which controls ACh release from the myenteric plexus. Chronic exposure to morphine does not produce specific changes in the muscarinic receptor mediating this inhibition.