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The 5‐HT 4 receptor subtype inhibits K + current in colliculi neurones via activation of a cyclic AMP‐dependent protein kinase
Author(s) -
Fagni L.,
Dumuis A.,
Sebben M.,
Bockaert J.
Publication year - 1992
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.1476-5381.1992.tb09087.x
Subject(s) - ketanserin , medicine , endocrinology , 5 ht receptor , receptor , receptor antagonist , biology , agonist , serotonin , staurosporine , protein kinase c , pharmacology , antagonist , signal transduction , biochemistry
1 The aim of the present study was to examine the effect of 5‐hydroxytryptamine (5‐HT) on K + current in primary culture of mouse colliculi neurones and to identify the 5‐HT receptor subtype that could be involved in this effect. 2 The voltage‐activated K + current of the neurones was partially blocked by 8‐bromo adenosine 3′:5′‐cyclic monophosphate (8‐bromo‐cyclic AMP). This effect was mimicked by 5‐HT and the action of 5‐HT could be antagonized by H7, a non specific protein kinase inhibitor, and by PKI, the specific cyclic AMP‐dependent protein kinase blocker. 3 A similar cyclic AMP‐dependent blockade of the K + current was found with renzapride (BRL 24 924) and other 5‐HT 4 receptor agonists such as cisapride, BIMU 8, zacopride and 5‐methoxytryptamine (5‐MeOT). ICS 205 930, the classical 5‐HT 4 receptor blocker, could not be used in this study because it inhibited the studied K + current by itself. However, the novel 5‐HT 4 receptor antagonist, DAU 6285 blocked the effects of 5‐HT and renzapride on the K + current. 4 The current was insensitive to the 5‐HT 1 and 5‐HT 3 receptor agonists (8‐hydroxy‐2‐(di‐n‐propylamino) tetralin, RU 24 969, carboxamidotryptamine, 2‐CH 3 ‐5‐HT) as well as to 5‐HT 1 , 5‐HT 2 and 5‐HT 3 antagonists (methiothepin, ketanserin, ondansetron [GR 38 032]). Moreover, these antagonists did not affect the actions of the tested 5‐HT 4 receptor agonists. 5 The present results show that part of the voltage‐activated K + current in mouse colliculi neurones is cyclic AMP‐sensitive and the blockade of the current by 5‐HT involves the 5‐HT 4 receptor subtype. The putative implication of 5‐HT 4 receptors in neuronal plasticity, via a blockade of K + channels, is discussed.