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5‐HT 4 receptor mediated facilitation of the emptying phase of the peristaltic reflex in the guinea‐pig isolated ileum
Author(s) -
Costall B.,
Naylor R.J.,
Tuladhar B.R.
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.tb14003.x
Subject(s) - methysergide , peristalsis , reflex , medicine , endocrinology , chemistry , anesthesia , serotonin , receptor
1 The influence of 5‐hydroxytryptamine (5‐HT) receptor agonists and antagonists on the emptying phase (circular muscle contraction) of the peristaltic reflex was investigated in the guinea‐pig isolated ileum. 2 The effect of drug application to the serosal surface was measured as the changes in threshold pressure required to trigger the peristaltic reflex and the interval between the peristaltic strokes. A facilitation or inhibition of peristalsis was defined as a reduction or increase in threshold pressure respectively. 3 Peristalsis was not modified by the inclusion of methysergide (1 μ m ) and/or ondansetron (2 μ m ) in the bathing medium. 5‐HT (0.1–1.0 μ m ) caused a facilitation of the perstaltic reflex; the response curve to 5‐HT was not altered by the presence of methysergide (1 μ m ) and ondansetron (2 μ m ). 4 In the presence of methysergide (1 μ m ) plus ondansetron (2 μ m ), 5‐HT (7.36 ± 0.06), 5‐methoxytryptamine (7.01 ± 0.17), 5‐carboxamidotryptamine (5.43 ± 0.06), renzapride (6.09 ± 0.17), ( S )‐zacopride (5.99 ± 0.11), ( R )‐zacopride (5.61 ± 0.13) and metoclopramide (4.8 ± 0.65) caused a concentration‐related facilitation of the peristaltic reflex, the pEC 50 values (mean ± s.e.mean) being shown in parentheses. 2‐Methyl‐5‐HT was ineffective up to 10 μ m . 5 The administration of SDZ 205–557 (1 μ m ) alone failed to modify the peristaltic reflex, but caused a parallel dextral shift in the concentration‐effect curve to 5‐HT (apparent pK B 7.38 ± 0.30). It failed to modify the effect of acetylcholine to enhance the peristaltic reflex. 6 It is concluded that the rank order of potency of the 5‐HT agonists from the indole and substituted benzamide series to facilitate the emptying phase of the peristaltic reflex in the guinea‐pig ileum closely correlates with their published actions as 5‐HT 4 agonists in other systems. An agonist action on the 5‐HT 4 receptor is also supported by the potency of the 5‐HT 3 /5‐HT 4 antagonist SDZ 205–557 (but not the 5‐HT 3 antagonist ondansetron) to inhibit the effects of 5‐HT.