Interaction of U-69,593 with. mu. -, delta- and k-opioid binding sites and its analgesic and intestinal effects in rats

Journal Article · Fri Jan 01 04:00:00 EST 1988 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(88)90638-8· OSTI ID:5726801

La Regina, A; Petrillo, P; Sbacchi, M; Tavani, A

The k-opioid compound U-69,593 was studied in rats in vitro in binding assays to assess its selectivity at the single types of opioid sites and in vivo to assess its analgesic activity and effect on intestinal propulsion. In vitro the U-69,593 inhibition curve of (/sup 3/H)-(-)-bremazocine binding suppressed at ..mu..- and delta-sites was biphasic and the inhibition constant (K/sub l/) at the high-affinity site (10-18nM) was two orders of magnitude smaller the K/sub l/ at the low-affinity site. The K/sub l/ at ..mu..- and delta-sites were respectively 3.3 and 8.5 ..mu..M. Thus (/sup 3/H)-(-)-bremazocine, suppressed at ..mu..- and delta-sites, may still bind more than one site, which U-69,593 might distinguish. In vivo U-69,593 i.p. prolonged the reaction time of rats on a 55/sup 0/C hot-plate and the dose of naloxone required to antagonize this effect was 40 times the dose that antagonized morphine-induced antinociception, suggesting the involvement of the k-receptor. In the intestinal transit test U-69,593 at doses between 0.5 and 15 mg/kg i.p. only slightly slowed intestinal transit of a charcoal meal in rats with no dose-relation; it partly but significantly antagonized morphine-induced constipation. These results suggest that the k-type of opioid receptor, with which U-69,593 interacts may induce analgesia, but has no appreciable role in the mechanisms of opioid-induced inhibition of intestinal transit in rats.

• Research Organization: Istituto di Richerche Farmacologiche Mario Negri, Milan, Italy
• OSTI ID: 5726801
• Journal Information: Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 42:3; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOASSAY
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BODY
CELL CONSTITUENTS
CELL MEMBRANES
DATA
DIGESTIVE SYSTEM
DRUGS
DYNAMIC FUNCTION STUDIES
ENDORPHINS
EXPERIMENTAL DATA
FUNCTIONS
GASTROINTESTINAL TRACT
IN VITRO
IN VIVO
INFORMATION
INHIBITION
INTESTINES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NEUROREGULATORS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES