Siriwardena A K, Budhoo M R, Smith E P, Kellum J M
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
J Surg Res. 1993 Jul;55(1):55-9. doi: 10.1006/jsre.1993.1108.
Having previously demonstrated that serotonin (5-HT)-induced chloride secretion in rat distal colon is mediated at both neural and nonneural receptors, we isolated the neural component of this response by adding the selective 5-HT3 receptor agonist, 2-methyl-5-hydroxytryptamine (2Me5HT), to in vitro sheets of rat distal colon with intact neural plexuses. Rats were sacrificed, and the distal colon excised, opened, cut into sections and mounted, all layers intact, as flat sheets in Ussing chambers under short-circuited conditions. 2Me5HT induced a prompt, significant (P < 0.01), concentration-dependent rise in short-circuit current (Isc; EC50 6.2 microM); 50 microM 2Me5HT decreased both net sodium and chloride absorption (-0.1 +/- 0.5 and -2.1 +/- 0.8 muEq/cm2 x hr, respectively); the difference (2.0 +/- 0.8 muEq/cm2 x hr) in these changes was not statistically different from the rise in Isc (1.5 +/- 0.3 muEq/cm2 x hr). Since the only significant change in unidirectional flux was the rise in electrogenic Cl- secretion (P < 0.01), the delta Isc induced by 2Me5HT may be used as a measure of electrogenic chloride secretion induced by the agonist. The rise in Isc induced by 2Me5HT was abolished by both 0.2 microM tetrodotoxin and 0.1 microM ICS 205-930 (a 5-HT3 antagonist) but was not inhibited by 1.0 M atropine 100 microM hexamethonium, 10 microM phentolamine, 10 microM propranolol, 10 microM 5-HTP-DP (a 5-HT1P antagonist), or 0.1 microM ketanserin (a 5-HT2 antagonist). These results indicate that 2-methyl-5-HT is a highly selective agonist for neurally based 5-HT3 receptors in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
先前已经证明，5-羟色胺（5-HT）诱导的大鼠远端结肠氯化物分泌是通过神经和非神经受体介导的，我们通过向具有完整神经丛的大鼠远端结肠体外薄片中添加选择性5-HT3受体激动剂2-甲基-5-羟色胺（2Me5HT）来分离该反应的神经成分。处死大鼠，切除远端结肠，打开，切成薄片并安装，所有层保持完整，在短路条件下作为扁平薄片置于尤斯灌流小室中。2Me5HT引起短路电流（Isc）迅速、显著（P < 0.01）且浓度依赖性升高（EC50为6.2 microM）；50 microM 2Me5HT使净钠和氯化物吸收均降低（分别为-0.1 +/- 0.5和-2.1 +/- 0.8微当量/平方厘米·小时）；这些变化的差值（2.0 +/- 0.8微当量/平方厘米·小时）与Isc的升高（1.5 +/- 0.3微当量/平方厘米·小时）在统计学上无显著差异。由于单向通量中唯一显著的变化是电生性Cl-分泌的增加（P < 0.01），2Me5HT诱导的ΔIsc可作为该激动剂诱导的电生性氯化物分泌的指标。2Me5HT诱导的Isc升高被0.2 microM河豚毒素和0.1 microM ICS 205-930（一种5-HT3拮抗剂）消除，但不被1.0 M阿托品、100 microM六甲铵、10 microM酚妥拉明、10 microM普萘洛尔、10 microM 5-HTP-DP（一种5-HT1P拮抗剂）或0.1 microM酮色林（一种5-HT2拮抗剂）抑制。这些结果表明，在该模型中，2-甲基-5-HT是基于神经的5-HT3受体的高度选择性激动剂。（摘要截短于250字）
