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Characterization of 5‐HT 3 receptors of N1E‐115 neuroblastoma cells by use of the influx of the organic cation [ 14 C]‐guanidinium
Author(s) -
Bönisch H.,
Barann M.,
Graupner J.,
Göthert M.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb12822.x
Subject(s) - chemistry , methysergide , ketanserin , veratridine , receptor , 5 ht receptor , agonist , guanidine , serotonin , endocrinology , pharmacology , biochemistry , sodium , biology , sodium channel , organic chemistry
1 The 5‐HT 3 receptor‐mediated cation influx into N1E‐115 mouse neuroblastoma cells has been studied by the use of the organic cation [ 14 C]‐guanidinium. 2 5‐Hydroxytryptamine (5‐HT, 30 μ m ) caused a time‐dependent influx of [ 14 C]‐guanidinium which, in contrast to the influx elicited by veratridine (100 μ m ), was not inhibited by tetrodotoxin (TTX, 10 μ m ). The 5‐HT‐induced influx was potentiated by substance P and inhibited by ondansetron. 3 5‐HT and the selective 5‐HT 3 receptor agonists, m ‐chloro‐phenylbiguanide, phenylbiguanide and 2‐methyl‐5‐HT caused bell‐shaped concentration‐response curves; the rank order of potency was m ‐chlorophenylbiguanide > 5‐HT > phenylbiguanide = 2‐methyl‐5‐HT. Among these agonists, 5‐HT elicited the highest influx of [ 14 C]‐guanidinium. 5‐Methoxytryptamine, an agonist at 5‐HT 4 receptors, showed no effect. 4 The [ 14 C]‐guanidinium influx induced by 100 μ m 5‐HT was not affected by methysergide (10 μ m ) and ketanserin (10 μ m ) but was inhibited by 5‐HT 3 receptor antagonists with the following rank order of potency: ICS 205–930 > ondansetron > MDL 72222 ≫ metoclopramide. 5 The 5‐HT‐induced [ 14 C]‐guanidinium influx was increased in the absence of Ca 2+ and/or Na + and by a reduction of the temperature from 36° to 20°C. 6 Preincubation with 5‐HT (100 μ m ) caused a time‐dependent and rapidly reversible decrease of the 5‐HT‐induced [ 14 C]‐guanidinium influx. 7 It is concluded that [ 14 C]‐guanidinium influx measurement in N1E‐115 cells is a convenient method to study properties of the cation channel of the 5‐HT 3 receptor. This influx is independent of the fast sodium channel.