Article date: January 1995
By: Shu‐Ichi Kojima, Yasuo Shimo, in Volume 114, Issue 1, pages 73-76
In the presence of atropine (0.2 μm) and indomethacin (2 μm), the effects of 5‐hydroxytryptamine (5‐HT) have been studied on electrically‐evoked, neurogenic contractions of the guinea‐pig proximal colon in vitro.
5‐HT, at higher concentrations than 1 nm, caused an increase in electrically (1 Hz, 0.3 ms, 160 mA)‐evoked, atropine‐resistant contractions in a concentration‐dependent manner and at 30 nm produced a maximal effect (pEC50 value of 8.20 ± 0.11, n = 6). The enhancing effects of 5‐HT on the electrically evoked contractions were mimicked by α‐methyl‐5‐HT (pEC50 value of 6.59 ± 0.05, n = 6).
Both hexamethonium (100 μm) and spantide (10 μm), selective antagonists for nicotinic and tachykinin receptors respectively, significantly reduced the enhancement of the electrically evoked contractions by 5‐HT (30 nm).
DAU 6285 (3 μm), a 5‐HT4 receptor antagonist, abolished the enhancing action of 5‐HT (30 nm), but metitepine (0.03 μm), a 5‐HT1/5‐HT2 receptor antagonist, ketanserin (0.01 μm), a 5‐HT2 receptor antagonist, and ondansetron (1 μm), a 5‐HT3 receptor antagonist, had no effect on the enhancement. The enhancing effects of a‐methyl‐5‐HT (1 μm) were also abolished by DAU 6285 (3 μm).
Both 5‐HT (30 nm) and α‐methyl‐5‐HT (1 μm) had no effect on contractions to exogenous substance P (0.15–0.3 nm).
These results indicate that in the guinea‐pig proximal colon, 5‐HT produced an enhancement of atropine‐resistant neurogenic contraction induced by electrical field stimulation through pre‐junctional mechanisms and that the enhancement is mediated by the stimulation of 5‐HT4 receptors located on intramural preganglionic cholinergic neurones and tachykininergic neurones.
In the presence of atropine (0.2 μm) and indomethacin (2 μm), the effects of 5‐hydroxytryptamine (5‐HT) have been studied on electrically‐evoked, neurogenic contractions of the guinea‐pig proximal colon in vitro.
5‐HT, at higher concentrations than 1 nm, caused an increase in electrically (1 Hz, 0.3 ms, 160 mA)‐evoked, atropine‐resistant contractions in a concentration‐dependent manner and at 30 nm produced a maximal effect (pEC50 value of 8.20 ± 0.11, n = 6). The enhancing effects of 5‐HT on the electrically evoked contractions were mimicked by α‐methyl‐5‐HT (pEC50 value of 6.59 ± 0.05, n = 6).
Both hexamethonium (100 μm) and spantide (10 μm), selective antagonists for nicotinic and tachykinin receptors respectively, significantly reduced the enhancement of the electrically evoked contractions by 5‐HT (30 nm).
DAU 6285 (3 μm), a 5‐HT4 receptor antagonist, abolished the enhancing action of 5‐HT (30 nm), but metitepine (0.03 μm), a 5‐HT1/5‐HT2 receptor antagonist, ketanserin (0.01 μm), a 5‐HT2 receptor antagonist, and ondansetron (1 μm), a 5‐HT3 receptor antagonist, had no effect on the enhancement. The enhancing effects of a‐methyl‐5‐HT (1 μm) were also abolished by DAU 6285 (3 μm).
Both 5‐HT (30 nm) and α‐methyl‐5‐HT (1 μm) had no effect on contractions to exogenous substance P (0.15–0.3 nm).
These results indicate that in the guinea‐pig proximal colon, 5‐HT produced an enhancement of atropine‐resistant neurogenic contraction induced by electrical field stimulation through pre‐junctional mechanisms and that the enhancement is mediated by the stimulation of 5‐HT4 receptors located on intramural preganglionic cholinergic neurones and tachykininergic neurones.
DOI: 10.1111/j.1476-5381.1995.tb14907.x
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