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Pharmacological analysis of 5‐hydroxytryptamine effects on electrically stimulated human isolated urinary bladder
Author(s) -
Corsi M.,
Pietra C.,
Toson G.,
Trist D.,
Tuccitto G.,
Artibani W.
Publication year - 1991
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.1476-5381.1991.tb12494.x
Subject(s) - methysergide , ketanserin , spiperone , ritanserin , metergoline , 5 ht receptor , chemistry , cisapride , endocrinology , lisuride , stimulation , medicine , serotonin , pharmacology , prazosin , antagonist , agonist , cyproheptadine , metoclopramide , receptor antagonist , receptor , dopamine agonist , vomiting
1 5‐Hydroxytryptamine (5‐HT) is able to potentiate the contractions induced by electrical field stimulation of pieces of human isolated urinary bladder. On the basis of available selective 5‐HT agonists and antagonists, we have further investigated the receptors involved and their site of action. 2 5‐HT produced a concentration‐dependent increase of the contractile response to electrical field stimulation from 0.1 n m to μ m . At higher concentrations (up to 100 μ m ) the effect decreased. These activities were mimicked by a variety of 5‐HT agonists, for which the following rank order of potency was found: 5‐HT > α‐methyl 5‐HT > 5‐methoxytryptamine > 5‐carboxamidotryptamine > 2‐methyl 5‐HT ≫ GR 43175. In addition the gastro‐prokinetics agents metoclopramide, cisapride and the 5‐HT 3 antagonist ICS 205–930 behaved as 5‐HT agonists, their EC 50 values being 2.3, 0.3, and 0.5 (μ m ) respectively. 3 The 5‐HT potentiating effect was resistant to antagonism by ondansetron (1 μ m ) and cyanopindolol (1 μ m ), selective 5‐HT 3 and 5‐HT 1A/1B antagonists respectively. The 5‐HT 2 antagonists ketanserin (1 μ m ), spiperone (1 μ m ) and methysergide (1 μ m ) also showed a weak inhibitory activity. Methiothepin (0.1–1 μ m ) antagonized only the inhibitory effect of 5‐HT. Metoclopramide (0.1–1 μ m ), cisapride (0.01–0.1 μ m ) and ICS 205–930 (0.3–3 μ m ) all produced a rightward displacement of the 5‐HT response curve with concomitant reduction of the maximum response. The pA 2 values calculated were 7.4, 8.5 and 7.0 respectively. The antagonism of metoclopramide was receptor specific and was not apparently related to interactions with dopaminergic activity since domperidone showed no antagonism of 5‐HT, and metoclopramide, itself, did not antagonize the potentiating effect of prostaglandin F 2α . 4 The receptor involved in the potentiating effect of 5‐HT may be located prejunctionally because 5‐HT did not potentiate responses to acetylcholine (ACh) or electrical field stimulation with the parameters of direct muscle excitation. Also, since the 5‐HT potentiating effect was blocked by atropine, it may be attributed to a release of ACh. 5 This study suggests that in the human urinary bladder 5‐HT causes two opposite effects on the contractile response to electrical field stimulation. A potentiating effect at low concentrations due to an interaction with an atypical receptor, different from the classical 5‐HT 1 , 5‐HT 2 or 5‐HT 3 subtypes and an inhibitory effect at greater concentrations probably due to an interaction with 5‐HT 1 ‐like receptors. The possibility that this atypical receptor possesses some characteristics of those found in other isolated preparations like guinea‐pig ileum, rat oesophagus and mouse embryo colliculi neurones is discussed.