Interaction of trimebutine and Jo-1196 (fedotozine) with opioid receptors in the canine ileum

Journal Article · Wed May 01 00:00:00 EDT 1991 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:5733354

Allescher, H D; Ahmad, S; Classen, M; Daniel, E E ^[1]

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1. Technical Univ., Munich, (West Germany)

Receptor binding of the opioid receptor antagonist, ({sup 3}H)diprenorphine, which has a similar affinity to the various opioid receptor subtypes, was characterized in subcellular fractions derived from either longitudinal or circular smooth muscle of the canine small intestine with their plexuses (myenteric plexus and deep muscular plexus, respectively) attached. The distribution of opioid binding activity showed a good correlation in the different fractions with the binding of the neuronal marker ({sup 3}H)saxitoxin but no correlation to the smooth muscle plasma membrane marker 5'-nucleotidase. The saturation data (Kd = 0.12 +/- 0.04 nM and maximum binding = 400 +/- 20 fmol/mg) and the data from kinetic experiments (Kd = 0.08 nmol) in the myenteric plexus were in good agreement with results obtained previously from the circular muscle/deep muscular plexus preparation. Competition experiments using selective drugs for mu (morphiceptin-analog (N-MePhe3-D-Pro4)-morphiceptin), delta (D-Pen2,5-enkephalin) and kappa (dynorphin 1-13, U50488-H) ligands showed the existence of all three receptor subtypes. The existence of kappa receptors was confirmed in saturation experiments using ({sup 3}H) ethylketocycloazocine as labeled ligand. Two putative opioid agonists, with effects on gastrointestinal motility, trimebutine and JO-1196 (fedotozin), were also examined. Trimebutine (Ki = 0.18 microM), Des-Met-trimebutine (Ki = 0.72 microM) and Jo-1196 (Ki = 0.19 microM) displaced specific opiate binding. The relative affinity for the opioid receptor subtypes was mu = 0.44, delta = 0.30 and kappa = 0.26 for trimebutine and mu = 0.25, delta = 0.22 and kappa = 0.52 for Jo-1196.

• OSTI ID: 5733354
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Vol. 257:2; ISSN 0022-3565
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
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AFFINITY
ANTIMETABOLITES
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LIGANDS
SMALL INTESTINE
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550201* - Biochemistry- Tracer Techniques