title: 5-Hydroxytryptamine3 receptor antagonism modulates a noxious visceral pseudoaffective reflex.
abstract: 5-Hydroxytryptamine (5-HT) receptor agonists and antagonists were dosed intravenously (i.v.) and studied for their effects on the depressor cardiovascular pseudoaffective reflex evoked by acute noxious colo-rectal distension in the anaesthetized rat. Methiothepin (100 micrograms kg-1) caused an initial, unsustained blockade of evoked depressor responses whilst ketanserin (100 micrograms kg-1) was without effect. By comparison, ondansetron dose dependently inhibited evoked depressor responses and was maximally active at 100 micrograms kg-1, causing a 57.5 +/- 0.9% reduction. An ID50 value of 36.7 micrograms kg-1 was estimated by regression analysis. In contrast, granisetron caused complete blockade of the depressor response with an ID50 of 0.4 microgram kg-1. Bell-shaped dose-effect curves were demonstrated for both granisetron and ondansetron. Intrathecal dosing with granisetron (100 ng) into the thoracolumbar region of the spinal cord prevented the depressor response to colo-rectal distension, suggesting a spinal site of action. The pseudoaffective depressor responses were not facilitated by pre-dosing with the 5-HT receptor agonists, 8-OH DPAT, alpha-methyltryptamine or 1-phenyl-biguanide. However, 8-OH DPAT (100 micrograms kg-1) facilitated pressor responses. It is suggested that 5-HT3-like receptors may have a role in modulating depressor responses to visceral pain and that in this action different 5-HT3 receptor antagonists are not necessarily equi-effective.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Harlow, Essex, U.K.
authors.forename: S E
authors.initials: SE
authors.lastname: Banner
authors.forename: M
authors.initials: M
authors.lastname: Carter
authors.forename: G J
authors.initials: GJ
authors.lastname: Sanger
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003106:Colon / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000502:physiology; D012018:Reflex / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists