RELATIONSHIP BETWEEN MUSCARINIC AUTOINHIBITION AND THE INHIBITORY EFFECT OF MORPHINE ON ACETYLCHOLINE-RELEASE FROM MYENTERIC PLEXUS OF GUINEA-PIG ILEUM

The relationship between muscarinic autoinhibition and the inhibitory effect of morphine on acetylcholine (ACh) release was investigated in a longitudinal muscle with myenteric plexus (LMMP) preparation of guin ea pig ileum. Morphine (10 mu M) inhibited spontaneous and evoked ACh release by electrical field stimulation (EFS) at 1 Hz but not at 10 Hz . Atropine (1 mu M) did not affect the resting ACh release, but it sig nificantly increased EFS-evoked release, suggesting activation of musc arinic autoreceptors by ACh released during EFS. Only when the autoinh ibition was weakened by atropine, morphine exhibited an inhibitory eff ect on the EFS-evoked release at 10 Hz. Bethanechol (300 mu M) inhibit ed the EFS-evoked release at 1 Hz but not 10 Hz, suggesting that musca rinic autoreceptors are partially or almost fully activated at 1 or 10 Hz stimulation, respectively. After bethanechol treatment, morphine d id not exhibit its inhibitory effect on the EFS-evoked release at 1 Hz . Naloxone (1 mu M) increased spontaneous and EFS-evoked ACh release a t 1 Hz but not at 10 Hz. Following treatment with atropine, naloxone a lso increased ACh release at 10-Hz stimulation. These results suggest that morphine and an endogenous opioid inhibit ACh release from LMMP p reparations when muscarinic autoinhibition mechanism does not fully wo rk. This inhibitory effect of morphine is discussed in relation to the calcium sensitivity of the preparations in ACh release.