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Effects of 5‐HT 3 receptor antagonists on 5‐HT and nicotinic depolarizations in guinea‐pig submucosal neurones
Author(s) -
Vanner S.,
Surprenant A.
Publication year - 1990
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.1476-5381.1990.tb13017.x
Subject(s) - hexamethonium , nicotinic agonist , 5 ht receptor , acetylcholine , depolarization , chemistry , postsynaptic potential , receptor , pharmacology , biology , endocrinology , serotonin , biochemistry
1 Intracellular recordings were made from neurones of the guinea‐pig submucosal plexus. The effects of several 5‐hydroxytryptamine 3 (5‐HT 3 ) receptor antagonists on depolarizations produced by ionophoretic application of 5‐HT and acetylcholine, as well as on fast excitatory postsynaptic potentials (fast e.p.s.ps) produced by nerve stimulation were examined. 2 ICS 205–930, GR 38032F, MDL 72222, cocaine and curare all inhibited the fast e.p.s.p. as well as the depolarizations in response to 5‐HT and acetylcholine (ACh) ionophoresis in a dose‐dependent fashion. 3 IC 50 values for ICS 205–930, GR 38032F, MDL 72222, cocaine and curare in inhibiting the 5‐HT mediated depolarizations were 12 n m , 100 n m , 3 μ m , 3 μ m and 20 μ m , respectively. 4 IC 50 values for ICS 205–930, GR 38032F, MDL 72222, cocaine and curare in inhibiting the nicotinic depolarizations were 4 μ m , 12 μ m , 11 μ m , 6 μ m and 17 μ m , respectively. Similar IC 50 values were obtained for inhibition of the fast e.p.s.ps by these antagonists. 5 The nicotinic receptor blocker, hexamethonium, inhibited the nicotinic depolarization and the fast e.p.s.p. with IC 50 values of 10 μ m . Hexamethonium (10 μ m ‐5 m m ) did not alter the depolarization induced by 5‐HT. 6 These results demonstrate that the pharmacological profile of 5‐HT 3 receptors present on submucosal neurones is identical to that of 5‐HT 3 receptors on myenteric neurones and, thus, provide evidence that the enteric neuronal 5‐HT 3 receptor forms a receptor subtype distinct from that characterized in other parts of the autonomic nervous system.