Opioids inhibit neuromuscular transmission in circular muscle of human and baboon jejunum.
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 delta-receptor antagonist. The selective delta agonist, cyclic [D-penicillamine2, D-penicillamine5]enkephalin, and the selective mu agonist, Try-Pro-NMePhe-D-Pro-NH2, (each 10 mumol/L) decreased inhibitory junction potential amplitude by 79% +/- 6.9% and 61% +/- 4.8%, respectively. The selective kappa agonist, [trans-3,4-dichloro-N-methyl-N-(2-91-pyrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate, (10 mumol/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 delta and mu 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 delta receptors.
Department of Physiology and Biophysics, Mayo Medical School, Rochester, Minnesota.
A J
AJ
Bauer
M G
MG
Sarr
J H
JH
Szurszewski
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D006801:Humans; D007583:Jejunum / Q000294:innervation*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D010215:Papio; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009435:Synaptic Transmission / Q000187:drug effects*
D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D004744:Enkephalin, Methionine; D004399:Dynorphins