Tetraethylammonium and 4-aminopyridine enhancement of 5-HT3 receptor-mediated contraction of guinea pig ileum in vitro.
OBJECTIVE
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.


CONCLUSIONS
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.
Yuan
Y M
YM
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Yang
H H
HH
Hu
G Y
GY
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009197:Myenteric Plexus / Q000187:drug effects; D015221:Potassium Channels; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology
D015221:Potassium Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014326:Tropanes; D012701:Serotonin; D019789:Tetraethylammonium; C045918:2-methyl-5-HT; D015761:4-Aminopyridine; C042253:bemesetron