Release of substance P by intrathecal KK-3, a newly synthesized Leu-enkephalin derivative.

Pharmacology, Biochemistry, and Behavior
M TakahashiH Kaneto

Abstract

Intrathecal (IT) injection of KK-3, a leucine-enkephalin analogue with weak, naloxone-reversible analgesic effect, produced behavior consisting of scratching, biting, licking and characteristic convulsion-like symptoms in mice. Naloxone or Mr2266 did not affect the behavior, suggesting a difference in the mechanisms for the production of the behavior and the analgesic effect. The behavior, except the convulsive symptom and the lag time of a couple of min for onset of the behavior, are quite similar to that elicited by IT substance P (SP). D-Pro2-D-Trp7,9-substance P, a SP antagonist, completely suppressed all the behavior induced by KK-3, indicating that the behavior is attributable to SP. By radioimmunoassay, it was found that SP was released by stimulation with KK-3 from the isolated spinal cord preparation of newborn rat. Intrathecal pretreatment with capsaicin, a depleter of SP, suppressed the KK-3-induced behavior, but did not affect the SP-evoked behavior. These results suggest that KK-3 acts as a releaser of SP in the spinal dorsal horn, and consequently produces SP-like behavior. Thus, a novel pharmacological action, the release of substance P from spinal cord by the IT injection of endogenous opioid peptide analogue, w...Continue Reading

References

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