Briejer M R, Akkermans L M, Meulemans A L, Lefebvre R A, Schuurkes J A
Department of Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Eur J Pharmacol. 1993 Nov 30;250(1):181-3. doi: 10.1016/0014-2999(93)90640-4.
The effects of three tachykinin NK1 receptor antagonists and a tachykinin NK2 receptor antagonist against substance P-induced contractions of the guinea-pig proximal colon longitudinal muscle were investigated. Atropine, tetrodotoxin and phosphoramidon did not affect the concentration-response curve for substance P (pEC50 = 7.8). The tachykinin NK1 receptor antagonist, 2S,3S-cis-CP 96345, competitively inhibited the contractions due to substance P (pA2 = 8.5; constrained pA2 = 8.9), but at higher concentrations (> or = 3 x 10(-7) M), 2S,3S-cis-CP 96345 also depressed the concentration-response curve for methacholine. The species-selective tachykinin NK1 receptor antagonists, WIN 51708 and WIN 62577 (both 1 x 10(-6) M), and the tachykinin NK2 receptor antagonist, SR 48968 (3 x 10(-7) M), had no effect. It is concluded that substance P induces contractions through the stimulation of tachykinin NK1 receptors on the smooth muscle cells. In this preparation, tachykinin NK2 receptors do not seem to be involved in the contractile action of substance P.
研究了三种速激肽NK1受体拮抗剂和一种速激肽NK2受体拮抗剂对P物质诱导的豚鼠近端结肠纵肌收缩的影响。阿托品、河豚毒素和磷酰胺素不影响P物质的浓度-反应曲线(pEC50 = 7.8)。速激肽NK1受体拮抗剂2S,3S-顺式-CP 96345竞争性抑制P物质引起的收缩(pA2 = 8.5;限定pA2 = 8.9),但在较高浓度(≥3×10⁻⁷ M)时,2S,3S-顺式-CP 96345也会压低乙酰甲胆碱的浓度-反应曲线。种属选择性速激肽NK1受体拮抗剂WIN 51708和WIN 62577(均为1×10⁻⁶ M)以及速激肽NK2受体拮抗剂SR 48968(3×10⁻⁷ M)均无作用。结论是P物质通过刺激平滑肌细胞上的速激肽NK1受体诱导收缩。在此制剂中,速激肽NK2受体似乎不参与P物质的收缩作用。