Yuan Y M, Xu D Y, Hu G Y
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Zhongguo Yao Li Xue Bao. 1998 Jan;19(1):31-5.
To study the effects of the K+ channel opener pinacidil on 5-HT3 receptor-mediated contractions of the isolated guinea pig ileum (GPI) longitudinal muscle-myenteric plexus strip preparations.
GPI contractions were recorded with a chart recorder through isometric transducers. The effect of pinacidil on binding properties of 5-HT3 receptors was assessed using [3H]GR65630 binding assay in membrane preparations of rat entorhinal cortex.
(1) A selective 5-HT3 receptor agonist 2-methyl-5-HT 0.1-300 mumol.L-1 and 5-HT 0.001-50 mumol.L-1 elicited GPI contractile responses in concentration-dependent manners, the EC50 values (and 95% confidence limits) for 2-methyl-5-HT and 5-HT were 10.0 (8.9-11.2) mumol.L-1 and 1.6 (1.3-1.9) mumol.L-1, respectively. Selective 5-HT3 receptor antagonist tropisetron 0.1 mumol.L-1 competitively inhibited the responses to 2-methyl-5-HT and 5-HT. (2) Pinacidil 0.5-5 mumol.L-1 inhibited 5-HT3 receptor-mediated contractions. (3) Pinacidil 1 mumol.L-1 enhanced the inhibitory effects of tropisetron 0.1 mumol.L-1 or another selective 5-HT3 receptor antagonist benesetron 1 mumol.L-1 on 5-HT-induced GPI contractile responses. (4) Pinacidil 1-5 mumol.L-1 did not affect GPI contractile responses evoked by a selective M-ACh receptor agonist carbachol 1 mumol.L-1. (5) Pinacidil 1-5 mumol.L-1 had no effect on binding properties of 5-HT3 receptors with selective 5-HT3 receptor radioligand [3H]GR65630 in the entorhinal cortex of rat brain.
The inhibition by pinacidil of 5-HT3 receptor-mediated GPI contractile responses may be mediated through activation of ATP-sensitive K+ channels located in prejunctional myenteric neurons.
研究钾通道开放剂吡那地尔对5-羟色胺3（5-HT3）受体介导的豚鼠离体回肠（GPI）纵行肌-肠肌丛肌条收缩的影响。
通过等长换能器用记录仪记录GPI的收缩情况。采用[3H]GR65630结合试验，在大鼠内嗅皮质膜制剂中评估吡那地尔对5-HT3受体结合特性的影响。
（1）选择性5-HT3受体激动剂2-甲基-5-HT 0.1～300μmol·L-1和5-HT 0.001～50μmol·L-1以浓度依赖方式引起GPI收缩反应，2-甲基-5-HT和5-HT的半数有效浓度（EC50）值（及95%置信限）分别为10.0（8.9～11.2）μmol·L-1和1.6（1.3～1.9）μmol·L-1。选择性5-HT3受体拮抗剂托烷司琼0.1μmol·L-1竞争性抑制对2-甲基-5-HT和5-HT的反应。（2）吡那地尔0.5～5μmol·L-1抑制5-HT3受体介导的收缩。（3）吡那地尔1μmol·L-1增强托烷司琼0.1μmol·L-1或另一种选择性5-HT3受体拮抗剂贝西司琼1μmol·L-1对5-HT诱导的GPI收缩反应的抑制作用。（4）吡那地尔1～5μmol·L-1不影响选择性M-乙酰胆碱受体激动剂卡巴胆碱1μmol·L-1诱发的GPI收缩反应。（5）吡那地尔1～5μmol·L-1对大鼠脑内嗅皮质中5-HT3受体与选择性5-HT3受体放射性配体[3H]GR65630的结合特性无影响。
吡那地尔对5-HT3受体介导的GPI收缩反应的抑制作用可能是通过激活位于节前肠肌神经元的ATP敏感性钾通道介导的。
