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 plexuslongitudinal 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, 0.5m s, supramaximal voltage) were inhibited by all the opioid peptides and morphine in a concentration-dependent manner. The order of potency was dynorphin-(1-13) > a-neo-endorphin > P-endorphin > [D-Ala2]-methionine-enkephalin >> aendorphin, methionine-enkephalin, leucine-enkephalin and morphine.3 The inhibitory actions of dynorphin-(1-13) (20 nM), cx-neo-endorphin (100 nM) and Pendorphin (3 jiM) were completely reversed either by naloxone (1 jiM) or by morphine (100 jiM). The Ke values of naloxone against dynorphin-(1-13) and a-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 x-neo-endorphin 462 times. 5 The inhibitory actions of dynorphin-(1-13) (100nM) and ac-neo-endorphin (300nM) 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±4.5nM. The contractile response of the oesophagus to acetylcholine was not affected by the pretreatment of the tissue with dynorphin-(1-13) (100 nM), a-neo-endorphin (300 nM) or P-endorphin (3 JiM).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 K-subtype.

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

“…For morphine, an inhibitory action on smooth, but not on striated, muscle contraction of the oesophagus, which was also reversible by naloxone, has been described in rat and guinea‐pig 15 . 22 Bieger et al . presented the possiblility that, for the rat oesophageal smooth muscle, the vagal efferents synapsing in submucosal ganglia represent the site of action for the opiate‐mediated inhibition but no possible receptor was characterized 15 .…”

Opioid receptor types on adrenergic nerve terminals of rabbit ear artery

“…DADL and [Met]enkephalin or [Leujenkephalin are known to show preference for the 6-receptor (Lord et al, 1977;Wister et al, 1979;Kosterlitz et al, 1980), while EKC and Dyn (1-13) show preference for the icreceptor (Huidobro-Toro et al, 1981;Oka et al, 1982b;Chavkin et al, 1982). Although a-Neoend acts on opioid receptors other than the Kand L-types in mouse vas deferens (Oka et al, 1982a), it acts as a Kagonist in guinea-pig ileum (Wister et al, 1981;Oka et al, 1982a), rabbit ileum and vas deferens (Oka et al, 1982a) and guinea-pig oesophagus (Kamikawa & Shimo, 1983). Judging from the activities of the opioids and opiates on rabbit ear artery, and from the reported agonist characteristics of the compounds, the opioid receptors in the ear artery seem to be of the 6and Ktypes; the 6-receptor being predominant.…”

“…However, since the rabbit ear artery, unlike the cerebral artery and mesenteric vascular smooth mus- known to show preference for the 6-receptor (Lord et al, 1977;Wister et al, 1979;Kosterlitz et al, 1980), while EKC and Dyn (1-13) show preference for the icreceptor (Huidobro-Toro et al, 1981;Oka et al, 1982b;Chavkin et al, 1982). Although a-Neoend acts on opioid receptors other than the K-and L-types in mouse vas deferens (Oka et al, 1982a), it acts as a Kagonist in guinea-pig ileum (Wister et al, 1981;Oka et al, 1982a), rabbit ileum and vas deferens (Oka et al, 1982a) and guinea-pig oesophagus (Kamikawa & Shimo, 1983).…”

Muscularis mucosae - the forgotten sibling

“…Also, morphine and opioid peptides inhibited the cholinergic neurotransmission via the activation of prejunctional κ-opioid receptors but lower concentrations of serotonin enhanced that by the activation of prejunctional 5-HT3 receptors Shimo,1983a;Kamikawa and Shimo, 1983b;Karim et al, 1996). Higher concentrations of serotonin produced a transient contraction of the muscularis mucosae which was abolished by the pretreatment with tetrodotoxin or atropine, indicating an indirect action via the stimulation of intramural cholinergic nerves (Bartlet, 1968b;Kamikawa and Shimo, 1983a).…”