title: Endomorphin-1 and -2, endogenous ligands for the mu-opioid receptor, inhibit striated and smooth muscle contraction in the rat oesophagus.
abstract: Recently, morphological evidence for an interaction of autonomic nerve fibres and extrinsic motor innervation of the rat oesophagus has emerged. The aim of the present study was to investigate the possible influence of endogenous and exogenous opioids on rat oesophageal smooth and striated muscle function in vitro. The entire oesophagus (excluding the lower oesophageal sphincter) with both Nervi (Nn) vagi, including the Nn recurrentes, was dissected and placed in an organ bath (100 mL, 37 degrees) with oxygenated Krebs-Ringer buffer. Contractile activity was measured in a longitudinal direction with a force transducer. Both Nn vagi were placed on a bipolar platinum electrode 2 cm distant from the oesophagus. Vagal stimulation (VS), applied for 1 s (40 V, 0.5 ms, 20 Hz) resulted in a biphasic contractile response that was completely blocked by 10(-6) M tetrodotoxin. The first part consisted of a tetanic striated muscle contraction, as it was abolished by tubocurarine (10(-5) M, n=5) but unaffected by atropine (10(-6) M, n=3) or hexamethonium (10(-4) M, n=4). In contrast, the second part was completely inhibited by hexamethonium (10(-4) M) and atropine (10(-6)M), whereas tubocurarine (10(-5) M) showed no influence, indicating a stimulation of preganglionic nerve fibres supplying oesophageal smooth muscle (muscularis mucosae) via relays in myenteric ganglia. In order to characterize opioid influence on the oesophageal striated and smooth muscle contractility, the following experiments were carried out. 10(-6) M endomorphin-1 and -2, endogenous mu-opioid-receptor agonists, reduced the contractile response of the striated (EM-2, -25.1+/-5.3%; n=16), and the smooth muscle (EM-2, -81.9+/-3.3%; n=11). Both effects were reversible by the opioid receptor antagonist naloxone (10(-6) M) and therefore, mediated via opioid receptors. Neither SNC-80, an agonist on the delta-opioid-receptor, U-69593, an agonist on the kappa-opioid-receptor, nor nociceptin, an agonist at the ORL1 (opioid receptor-like) receptor, had a significant effect on the striated muscle contraction. In contrast to SNC-80, U-69593 and nociceptin inhibited smooth muscle contraction but this relaxation could not be antagonized by naloxone. None of the opioid receptor antagonists used had an effect on basal tonus or muscle contraction following VS. Our data provide evidence for an autonomic modulation of vagal motor innervation of the striated and smooth oesophageal muscle. Endomorphin-1 and -2, both selective mu-opioid receptor agonists, cause an inhibition of striated and smooth muscle response which is reversible by naloxone, an opioid receptor antagonist. The location of the mu-opioid receptor still has to be established.
authors.affiliation: GAP, Department of Internal Medicine II, Technical University Munich, FRG.
authors.forename: M
authors.initials: M
authors.lastname: Storr
authors.forename: F
authors.initials: F
authors.lastname: Geisler
authors.forename: W L
authors.initials: WL
authors.lastname: Neuhuber
authors.forename: V
authors.initials: V
authors.lastname: Schusdziarra
authors.forename: H D
authors.initials: HD
authors.lastname: Allescher
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C105294:endomorphin 2