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

Abstract

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. 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. 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 Ke values of naloxone against dynorphin‐(1–13) and α‐neo‐endorphin were 30 and 25 nm, respectively. 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. 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). 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). 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. 1983 British Pharmacological Society