Pharmacological characterization of the opioid receptor in the submucous plexus of the guinea-pig oesophagus.
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) greater than alpha-neo-endorphin greater than beta-endorphin greater than [D-Ala2]-methionine-enkephalin much greater than alpha-endorphin, methionine-enkephalin, leucine-enkephalin and morphine. 3 The inhibitory actions of dynorphin-(1-13) (20 nM), alpha-neo-endorphin (100 nM) and beta-endorphin (3 microM) were completely reversed either by naloxone (1 microM) or by morphine (100 microM). The Ke values of naloxone against dynorphin-(1-13) and alpha-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 alpha-neo-endorphin 462 times. 5 The inhibitory actions of dynorphin-(1-13) (100 nM) and alpha-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), alpha-neo-endorphin (300 nM) or beta-endorphin (3 microM). 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 kappa-subtype.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004723:Endorphins / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D004947:Esophagus / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009092:Mucous Membrane / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*
D004723:Endorphins; D004745:Enkephalins; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine; D000109:Acetylcholine