Antagonism of kappa opioid mediated effects in the rat by cyclo(Leu-Gly)

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Life Sciences; (USA)

DOI:https://doi.org/10.1016/0024-3205(89)90235-X· OSTI ID:6855638

Bhargava, H N; Ramarao, P ^[1]

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1. Univ. of Illinois, Chicago (USA)

The effect of cyclo(Leu-Gly) on U-50,488H- induced pharmacological actions was determined in male Sprague-Dawley rats. Intraperitoneal (i.p.) administration of U-50,488H to rats produced analgesia (tail-flick) and increased urinary output. Cyclo (Leu-Gly) antagonized the analgesic response to U-50,488H. A dose of 10 mg/kg (i.p.) of U-50,488H increased the spontaneous urinary output which was anatagonized by cyclo (Leu-Gly). To determine whether cyclo (Leu-Gly) was acting as a kappa-opioid receptor antagonist, the effect of cyclo (Leu-Gly) on the binding of ({sup 3}H) ethylketocyclazoncine (EKC) to membranes of rat cerebral cortex and spinal cord was determined. The IC{sub 50} values of cyclo(Leu-Gly) in displacing ({sup 3}H)EKC from its binding sites in cortex and spinal cord were 1.44 and 0.40 mM, respectively. Chronic administration of U-50,488H for 4 days induced tolerance to its analgesic effect. The latter was not affected by cyclo(Leu-Gly) given once a day for 4 days. It is concluded that cyclo(Leu-Gly) antagonizes acute actions of U-50,488H and that such effects of cyclo(Leu-Gly) are not mediated via a direct action on kappa-opioid receptors.

• OSTI ID: 6855638
• Journal Information: Life Sciences; (USA), Journal Name: Life Sciences; (USA) Vol. 45:26; ISSN 0024-3205; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CEREBRAL CORTEX
CEREBRUM
DRUGS
ENDORPHINS
HYDROGEN COMPOUNDS
INJECTION
INTAKE
INTRAPERITONEAL INJECTION
ISOTOPE APPLICATIONS
KINETICS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PROTEINS
REACTION KINETICS
RECEPTORS
SPINAL CORD
TRACER TECHNIQUES
TRITIUM COMPOUNDS