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Differences between 5‐HT 3 receptor antagonists in modulation of visceral hypersensitivity
Author(s) -
Banner S.E.,
Sanger G.J.
Publication year - 1995
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.1476-5381.1995.tb13263.x
Subject(s) - granisetron , ondansetron , distension , medicine , tropisetron , visceral pain , reflex , anesthesia , 5 ht3 receptor , nociception , antiemetic , serotonin , 5 ht receptor , endocrinology , receptor , vomiting
1 Noxious colo‐rectal distension was applied in conscious rats by acute balloon inflation and the effects observed as abdominal muscle contraction with the threshold typically between 10–40 mmHg. The effects of 5‐HT 3 receptor antagonists on responses to noxious colo‐rectal distension were then studied in both normal rats and those pretreated with 5‐hydroxytryptophan (5‐HTP). 2 Granisetron and ondansetron (10 μg kg −1 and 1 mg kg −1 , s.c.) had no effect on visceromotor thresholds to colo‐rectal distension in normal rats. 3 Hypersensitivity of the colo‐rectum was achieved by systemic administration of a low dose of 5‐HTP (10 mg kg −1 , s.c.) which lowered the distension pressure required to induce the visceromotor reflex; analysis of variance showed a highly significant treatment effect ( F 1,11 = 84.26, P <0.001). 4 Granisetron, zatosetron, bemesetron and renzapride equi‐potently increased the threshold values at which distension evoked a visceromotor reflex after dosing with 5‐HTP, with a maximal response 3.6 to 4.2 fold above saline controls, at 10 μg kg −1 , s.c. Metoclopramide (10 μg kg −1 ) also raised the level of distension required to elicit a response. By comparison, tropisetron caused a small, non‐significant increase in visceromotor threshold values and only at high doses (1 mg kg −1 ), whilst ondansetron and BRL 46470 had no signficant effects at doses up to 10 mg kg −1 . 5 The response to granisetron (10 μg kg −1 , s.c.) in 5‐HTP‐treated rats was unaltered by pre‐administration of naloxone (5 mg kg −1 , s.c). 6 These results suggest that a 5‐HT 3 ‐like receptor modulates 5‐HTP‐ evoked visceral hypersensitivity. However, the rank order of antagonist potency does not correlate with their order of potency against the classically defined 5‐HT 3 receptor.