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  • Title: Tetraethylammonium and 4-aminopyridine enhancement of 5-HT3 receptor-mediated contraction of guinea pig ileum in vitro.
    Author: Yuan YM, Yang HH, Hu GY.
    Journal: Zhongguo Yao Li Xue Bao; 1998 Sep; 19(5):451-5. PubMed ID: 10375808.
    Abstract:
    AIM: To study the effects of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on 5-HT3 receptor-mediated contractions of the isolated guinea pig ileum longitudinal muscle-myenteric plexus strip preparations (GPI). METHODS: GPI contractions were recorded with a chart recorder through isometric transducers. The effect of TEA and 4-AP on binding properties of 5-HT3 receptors was assessed using [3H]GR65630 binding assay in membrane preparation of rat entorhinal cortex. RESULTS: (1) Both TEA 0.5 mmol.L-1 and 4-AP 5 mumol.L-1 increased the spontaneous activity, and elicited contractions of GPI; atropine 10 mumol.L-1 or the selective 5-HT3 receptor antagonist MDL72222 100 mumol.L-1 prevented these effects. (2) Both TEA 0.05-0.5 mmol.L-1 and 4-AP 1-10 mumol.L-1 enhanced GPI contractions induced by the selective 5-HT3 receptor agonists 2-methyl-5-HT in concentration-dependent manners. (3) Both TEA 0.5 mmol.L-1 and 4-AP 5 mumol.L-1 attenuated the inhibitory effects of the selective 5-HT3 receptor antagonists tropisetron 0.1 mumol.L-1 and benesetron 1 mumol.L-1 on 5-HT3 receptor-mediated GPI contractions. (4) Neither TEA 0.1-0.5 mmol.L-1 nor 4-AP 5-10 mumol.L-1 affected GPI contractions evoked by the selective M-ACh receptor agonist carbachol 1 mumol.L-1. (5) TEA 0.5 mmol.L-1 and 4-AP 10 mumol.L-1 had no effect on the properties of binding of the selective 5-HT3 receptor radioligand [3H]GR65630 to 5-HT3 receptors. CONCLUSION: The enhancement by TEA and 4-AP of 5-HT3 receptor-mediated GPI contractile responses was due to blocking K+ channels in prejunctional myenteric neurons.
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