Delta-opioid receptor agonists inhibit neuromuscular transmission in human colon.
The present study was undertaken to investigate the possible role of delta-opioid receptors in the neuroregulation of human colonic motility by using a superfusion model. Spontaneous mechanical activity and responses to electrical transmural nerve stimulation of both longitudinal and circular muscle strips from the human sigmoid colon were studied. Exogenously added delta-opioid receptor agonists did not modify spontaneous contractile activities of either type of strip. Nerve stimulation induced a triphasic response composed of an initial contraction followed by a relaxation and an off-contraction. This response was mediated by cholinergic excitatory nerves and non-adrenergic, non-cholinergic excitatory and inhibitory nerves. [Met5]Enkephalin and the synthetic delta-opioid receptor agonist [D-Pen2,D-Pen5]enkephalin (DPDPE) significantly decreased the amplitude of the initial contraction and of the off-contraction. The effects of both delta-opioid receptor agonists were reduced in the presence of either the delta-opioid receptor antagonist, ICI 174864, or another delta-opioid receptor antagonist, naltrindole. ICI 174864 prevented neither the effects of a natural kappa-opioid receptor agonist, dynorphin-(1-13) nor those of the mu-opioid receptor agonist, PL017. Therefore, these data suggest that delta-opioid receptors might be involved in the neuroregulation of smooth muscle of human colon and may mediate inhibition of cholinergic and non-cholinergic excitatory transmission within the myenteric plexus.
Chamouard
P
P
INSERM U381, Strasbourg, France.
Rohr
S
S
Meyer
C
C
Baumann
R
R
Angel
F
F
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000294:innervation; D004399:Dynorphins / Q000494:pharmacology; D004558:Electric Stimulation; D004723:Endorphins / Q000008:administration & dosage / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000008:administration & dosage / Q000494:pharmacology; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists*; D009435:Synaptic Transmission / Q000187:drug effects*
D000700:Analgesics; D000701:Analgesics, Opioid; D004723:Endorphins; D004745:Enkephalins; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D017465:Receptors, Opioid, delta; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D009271:Naltrexone; C026843:dynorphin (1-13); D004399:Dynorphins; C044708:morphiceptin, N-Me-Phe(3)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; C055382:naltrindole