Pharmacological characterization of the opioid receptor in the submucous plexus of the guinea‐pig oesophagus

Abstract

1 The cholinergically mediated electrically-induced contractions of the submucous plexus-longitudinal muscularis mucosae preparation of the guinea-pig oesophagus were used to study the actions of opioid peptides and morphine. 2 The twitch contractions of the tissue (0.1 Hz, 0.5 ms, supramaximal voltage) were inhibited by all the opioid peptides and morphine in a concentration-dependent manner. The order of potency was dynorphin-(1–13) > α-neo-endorphin > β-endorphin > [d-Ala²]-methionine-enkephalin ≪≪ α-endorphin, methionine-enkephalin, leucine-enkephalin and morphine. 3 The inhibitory actions of dynorphin-(1–13) (20 nm), α-neo-endorphin (100 nm) and β-endorphin (3 μm) were completely reversed either by naloxone (1 μm) or by morphine (100 μm). The K_e values of naloxone against dynorphin-(1–13) and α-neo-endorphin were 30 and 25 nm, respectively. 4 Increasing the concentration of calcium from 1.8 to 3.6 mm in Tyrode solution decreased the sensitivity of the tissue to dynorphin-(1–13) 7.4 times and to α-neo-endorphin 462 times. 5 The inhibitory actions of dynorphin-(1–13) (100 nm) and α-neo-endorphin (300 nm) were inversely related to stimulus frequency, being most active at low frequencies (0.1–1 Hz), and least active at high (30 Hz). 6 Exogenously applied acetylcholine produced concentration-dependent contractions of the isolated muscularis mucosae, with an EC₅₀ of 72.6 ± 4.5 nm. The contractile response of the oesophagus to acetylcholine was not affected by the pretreatment of the tissue with dynorphin-(1–13) (100 nm), α-neo-endorphin (300 nm) or β-endorphin (3 μm). 7 It is concluded that the submucous plexus-longitudinal muscularis mucosae of the guinea-pig oesophagus is inhibited by opioid peptides acting at prejunctional opioid receptors, probably of the κ-subtype.