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KCI등재 학술저널

5-Hydroxytryptamine Generates Tonic Inward Currents on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

5-Hydroxytryptamine Generates Tonic Inward Currents on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

In this study we determined whether or not 5-hydroxytryptamine (5-HT) has an effect on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of 5-HT on pacemaker activities were investigated using a whole-cell patch-clamp technique, intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>) analysis, and RT-PCR in ICC. Exogenously-treated 5-HT showed tonic inward currents on pacemaker currents in ICC under the voltage-clamp mode in a dose-dependent manner. Based on RT-PCR results, we found the existence of 5-HT<sub>2B, 3, 4, and 7</sub> receptors in ICC. However, SDZ 205557 (a 5-HT<sub>4</sub> receptor antagonist), SB 269970 (a 5-HT<sub>7</sub> receptor antagonist), 3-tropanylindole &#8722; 3 &#8722; carboxylate methiodide (3-TCM; a 5-HT<sub>3</sub> antagonist) blocked the 5-HT-induced action on pacemaker activity, but not SB 204741 (a 5-HT<sub>2B</sub> receptor antagonist). Based on [Ca<sup>2+</sup>]<sub>i</sub> analysis, we found that 5-HT increased the intensity of [Ca<sup>2+</sup>]<sub>i</sub>. The treatment of PD 98059 or JNK II inhibitor blocked the 5-HT-induced action on pacemaker activity of ICC, but not SB 203580. In summary, these results suggest that 5-HT can modulate pacemaker activity through 5-HT<sub>3, 4, and 7 </sub>receptors via [Ca<sup>2+</sup>]<sub>i</sub> mobilization and regulation of mitogen-activated protein kinases.

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