Release of substance P by intrathecal KK-3, a newly synthesized Leu-enkephalin derivative.
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, was demonstrated.
Takahashi
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
Tokuyama
S
S
Kaneto
H
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D004151:Dipeptides; D013373:Substance P; D009270:Naloxone; C062633:KK 3; D002211:Capsaicin