Opioids inhibit neuromuscular transmission in circular muscle of human and baboon jejunum

Abstract

Intracellular recording techniques were used to study the effects of methionine enkephalin and dynorphin(1-13) on normal circular smooth muscle of human and baboon jejunum. Tetrodotoxin-sensitive inhibitory junction potentials had a mean (±SEM) amplitude of 21 ± 3.3 mV in human jejunum and 24.1 ± 1.3 mV in baboon jejunum. In both species, exogenously added methionine enkephalin and dynorphin (1-13) decreased inhibitory junction potentials amplitude in a dose-dependent manner with methionine enkephalin being more potent. Both opioid peptides acted on receptors located on axons of intrinsic inhibitory nerves. The effects of both methionine enkephalin and dynorphin(1-13) were blocked by ICI-174,864, a selective δ-receptor antagonist. The selective δ agonist, cyclic [d-penicil-lamine2, d-penicillamine5]enkephalin, and the selective μ agonist, Try-Pro-NMePhe-d-Pro-NH2, (each 10 μmol/L) decreased inhibitory junction potential amplitude by 79% ± 6.9% and 61% ± 4.8%, respectively. The selective k agonist, [trans-3,4-dichloro-N-methyl-N-(2-91-pyrolidinyl)-cyclohexyl]-benzene-acetamide methanesulfonate, (10 μmol/L) had no effect. Although direct postsynaptic opioid receptor blockade of the inhibitory neurotransmitter on the smooth muscle cell has not been ruled out, the authors believe these data suggest that δ and μ receptors were present on inhibitory motor nerves innervating the circular muscle and that methionine enkephalin and dynorphin(1-13) decreased release of inhibitory neurotransmitter(s) by acting on δ receptors. © 1991.