mr-2266 and beta-neo-endorphin

Smooth muscle cells isolated separately from the longitudinal and circular muscle layers of guinea pig and human intestine exhibited a unique pattern of response to derivatives of proenkephalin and prodynorphin present in the myenteric plexus. Receptors for other myenteric transmitters (acetylcholine, the octapeptide of cholecystokinin and substance P) capable of mediating contraction, were present on both circular and longitudinal muscle cells, whereas opiate receptors were present on circular muscle cells and selectively absent from longitudinal muscle cells in both species. The opiate myoreceptors belonged to the three main subclasses (kappa, delta and mu) and exhibited a rank order of sensitivity similar to that of opiate neuroreceptors. The distribution of these receptors parallels the distribution of opioid nerve fibers and appears to reflect the role of opioids in the regulation of neuromuscular activity.

Topics: Acetylcholine; Animals; Atropine; Benzomorphans; beta-Endorphin; Dose-Response Relationship, Drug; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Guinea Pigs; Humans; Jejunum; Muscle Contraction; Muscle, Smooth; Naloxone; Peptide Fragments; Proglumide; Receptors, Opioid; Sincalide

The choice of opiate receptor subtype by alpha- and beta-neo-endorphin was studied in isolated preparations. Neo-endorphins had significant inhibitory actions on the electrically evoked contractions of guinea-pig ileum, mouse vas deferens and rabbit ileum as well as on the rabbit vas deferens which had been shown to contain kappa-receptors exclusively. Mr 2266, a relatively specific kappa-receptor antagonist, was more effective than naloxone, a relatively mu-receptor antagonist, to antagonize the agonist actions of neo-endorphins in either the guinea-pig and rabbit ileum or in the rabbit vas deferens. By contrast, in the mouse vas deferens, the effectiveness of Mr 2266 to antagonize the agonist actions of neo-endorphins was low and similar to that of naloxone. The potencies of neo-endorphins relative to that of ethylketocyclazocine, a representative kappa-receptor agonist, in the guinea-pig ileum were similar to those in the rabbit ileum but were significant different from those in the mouse vas deferens. The data indicate that neo-endorphins act as kappa-receptor agonists in either the guinea-pig and rabbit ileum or in the rabbit vas deferens while in the mouse vas deferens they act on opiate receptor subtypes other than kappa- and mu-receptors.

Topics: Animals; Benzomorphans; beta-Endorphin; Cyclazocine; Drug Interactions; Endorphins; Enkephalins; Ethylketocyclazocine; Guinea Pigs; Ileum; In Vitro Techniques; Muscle Contraction; Muscle, Smooth; Naloxone; Protein Precursors; Rabbits; Receptors, Opioid