Phorbol ester suppression of opioid analgesia in rats
- Beijing Medical Univ. (China)
Protein kinase C (PKC) has been shown to be an important substrate in intracellular signal transduction. Very little is known concerning its possible role in mediating opiate-induced analgesia. In the present study, 12-O-tetradecanoylphorbol 13-acetate (TPA), a selective activator of PKC, was injected intrathecally (ith) to assess its influence on the analgesia induced by intrathecal injection of the mu opioid agonist PL017, the delta agonist DPDPE and the kappa agonist 66A-078. Radiant heat-induced tail flick latency (TFL) was taken as an index of nociception. TPA in the dose of 25-50 ng, which did not affect the baseline TFL, produced a marked suppression of opioid antinociception, with a higher potency in blocking mu and delta than the kappa effect. In addition, mu and delta agonists induced remarkable decreases in spinal cyclic AMP (cAMP) content whereas the kappa effect was weak. The results suggest a cross-talk between the PKC system and the signal transduction pathway subserving opioid analgesia.
- OSTI ID:
- 6034738
- Journal Information:
- Life Sciences; (USA), Vol. 47:19; ISSN 0024-3205
- Country of Publication:
- United States
- Language:
- English
Similar Records
Opioid binding sites in the guinea pig and rat kidney: Radioligand homogenate binding and autoradiography
Stereospecific effects of morphine on plasma opioid peptide levels and nociception in dogs
Related Subjects
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PHOSPHOTRANSFERASES
BIOLOGICAL FUNCTIONS
AMP
ANTIMETABOLITES
BIOLOGICAL PATHWAYS
NEUROREGULATORS
RATS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARCINOGENS
DRUGS
ENZYMES
ESTERS
FUNCTIONS
MAMMALS
NUCLEOTIDES
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
RODENTS
TRANSFERASES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology