Dermorphin analogueであるH-Tyr-D-Arg-Phe-β-Ala-OHおよびH-Tyr-D-Arg-Phe-β-Ala-NH_2によるcapsaicinおよびsubstance P誘発性SBL行動抑制の違いについて

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Intrathecal (i.t.) administration of substance P or capsaicin elicited a characteristic behavioural response consisting of scratching, biting and licking (SBL) in mice. The behavioural response induced by substance P or capsaicin was almost completely inhibited by simultaneous i. t. injection of [D-Ala^2, MePhe^4, Gly(ol)^5] enkephalin (DAMGO), H-Tyr-D-Arg-Phe-β-Ala-OH (TAPA) or H-Tyr-D-Arg-Phe-β-Ala-NH_2 (TAPA-NH_2). Pretreatment with naloxonazine significantly antagonized inhibitory action of TAPA-NH_2 on substance Pinduced SBL behavioural response without antagonistic effect against DAMGO and TAPA, while antinociceptive effect of DAMGO, TAPA and TAPA-NH_2 was completely inhibited by the pretreatment with naloxone. TAPA-induced antinociception but not DAMGO-and TAPA-NH_2-induced antinociception on behavioural response produced by i. t. capsaicin was completely inhibited by the pretreatment with naloxonazine, whereas naloxone at a dose of 1 mg/kg s. c. completely antagonized the antinociceptive effect of i. t. co-administered TAPA, DAMGO- or TAPA-NH_2. These results led us to understanding of differential action mechanism of TAPA- and TAPA-NH_2-induced antinociception, as assayed by SBL behavioural response produced by both capsaicin and substance P.
東北薬科大学の論文