Relationship Between Inhibitory Effect of Endogenous Opioid via Mu-Receptors and Muscarinic Autoinhibition in Acetylcholine Release From Myenteric Plexus of Guinea Pig Ileum

Abstract

Relationship between activation of opioid receptors and muscarinic autoinhibition in acetylcholine (ACh) release from the myenteric plexus was studied in longitudinal muscle myenteric plexus (LMMP) preparations of guinea pig ileum. A mu-receptor agonist, [D-Ala2, N-Me-Phe4, Gly5-ol] enkephalin (DAMGO), at a concentration of 1 μM inhibited the ACh release evoked by electrical field stimulation (EFS) at 1 Hz but not at 10 Hz. After the muscarinic autoreceptors were blocked with atropine (1 μM), DAMGO inhibited EFS-evoked ACh release also at 10 Hz. After the autoreceptors were potently activated with muscarine (200 μM), the inhibitory effect of DAMGO at 1 Hz was abolished. A kappa-receptor agonist, U-50,488, at 1 μM inhibited the EFS-evoked ACh release both at 1 and 10 Hz. U-50,488 inhibited ACh release regardless of the presence of atropine or muscarine. A delta-agonist, enkephalin [D-PEN2,5] (PDPDE), did not show any significant effect. On the other hand, a selective mu-receptor antagonist, cyprodime, increased ACh release evoked by EFS at 1 Hz, but not at 10 Hz. After the autoreceptors were blocked, cyprodime increased EFS-evoked ACh release also at 10 Hz. The selective kappa-receptor antagonist, nor-binaltorphimine, did not affect ACh release in the absence or presence of atropine. The results suggest that endogenous opioid(s) inhibits ACh release by activating mu-, but not kappa- and delta-receptors in the LMMP of guinea pig ileum and that the inhibitory effect of endogenous opioid(s) in the ACh release is important when muscarinic autoinhibition mechanism does not fully work.