Endomorphin-1 and-2, endogenous ligands for the mu-opioid receptor, inhibit striated and smooth muscle contraction in the rat oesophagus

Recently morphological evidence for an interaction of autonomic nerve fibre s and extrinsic motor innervation of the rat oesophagus has emerged. The ai m of the present study was to investigate the possible influence of endogen ous and exogenous opiolds on rat oesophageal smooth and striated muscle fun ction in vitro. The entire oesophagus (excluding the lower oesophageal sphi ncter) with both Nervi (Nn) vagi, including the Nn recurrentes, was dissect ed and placed in an organ bath (100 mt, 37 degrees) with oxygenated Krebs-R inger buffer. Contractile activity was measured in a longitudinal direction with a force transducer. Both Nn vagi were placed on a bipolar platinum el ectrode 2 cm distant from the oesophagus. Vagal stimulation (VS), applied f or 1 s (40 V, 0.5 ms, 20 Hz) resulted in a biphasic contractile response th at was completely blocked by 10(-6) Mi tetrodotoxin. The first part consist ed of a tetanic striated muscle contraction, as it tvas abolished by tubocu rarine (10(-5) M, n = 5) but unaffected by atropine (10(-6) M, n=3) or hexa methonium (10(-4) M, n=4). In contrast, the second part was completely inhi bited by hexamethonium (10(-4) ivr) and atropine (10(-6) M), whereas tubocu rarine (10(-5) M) showed no influence, indicating a stimulation of pre gang lionic nerve fibres supplying oesophageal smooth muscle (muscularis mucosae ) via relays in myenteric ganglia. In order to characterize opioid influenc e on the oesophageal striated and smooth muscle contractility, the followin g experiments were carried out. 10(-6) M endomorphin-1 and -2, endogenous m u-opioid-receptor agonists, reduced the contractile response of the striate d (EM-2, -25.1 +/- 5.3%; n=16), and the smooth muscle (EM-2, - 82.9 +/- 3.3 %; n=11). Both effects were reversible by the opioid receptor antagonist na loxone (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 ka ppa-opioid-receptor, nor nociceptin, an agonist at the ORL1 (opioid recepto r-like(1)) receptor, had a significant effect on the striated muscle contra ction. In contrast to SNC-80, U-69593 and nociceptin inhibited smooth muscl e contraction but this relaxation could not be antagonized by naloxone. Non e of the opioid receptor antagonists used had an effect on basal tonus or m uscle contraction following VS. Our data provide evidence for an autonomic modulation of vagal motor innervation of the striated and smooth oesophagea l muscle. Endomorphin-1 and -2, both selective mu-opioid receptor agonists, cause an inhibition of striated and smooth muscle response which is revers ible by naloxone, an opioid receptor antagonist. The location of the mu-opi oid receptor still has to be established.