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Pharmacological profile of the 5‐HT‐induced inhibition of cardioaccelerator sympathetic outflow in pithed rats: correlation with 5‐HT 1 and putative 5‐ht 5A/5B receptors
Author(s) -
SánchezLópez Araceli,
Centurión David,
Vázquez Erika,
Arulmani Udayasankar,
Saxena Pramod R,
Villalón Carlos M
Publication year - 2003
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 - 10.1038/sj.bjp.0705489
Subject(s) - ritanserin , medicine , endocrinology , methysergide , yohimbine , 5 ht receptor , prazosin , pharmacology , 5 ht1 receptor , tropisetron , serotonin , receptor , chemistry , antagonist
Continuous infusions of 5‐hydroxytryptamine (5‐HT) inhibit the tachycardiac responses to preganglionic (C 7 ‐T 1 ) sympathetic stimulation in pithed rats pretreated with desipramine. The present study identified the pharmacological profile of this inhibitory action of 5‐HT. The inhibition induced by intravenous (i.v.) continuous infusions of 5‐HT (5.6 μ g kg −1 min −1 ) on sympathetically induced tachycardiac responses remained unaltered after i.v. treatment with saline or the antagonists GR 127935 (5‐HT 1B/1D ), the combination of WAY 100635 (5‐HT 1A ) plus GR 127935, ritanserin (5‐HT 2 ), tropisetron (5‐HT 3/4 ), LY215840 (5‐HT 7 ) or a cocktail of antagonists/inhibitors consisting of yohimbine ( α 2 ), prazosin ( α 1 ), ritanserin, GR 127935, WAY 100635 and indomethacin (cyclooxygenase), but was abolished by methiothepin (5‐HT 1/2/6/7 and recombinant 5‐ht 5A/5B ). These drugs, used in doses high enough to block their respective receptors/mechanisms, did not modify the sympathetically induced tachycardiac responses per se . I.v. continuous infusions of the agonists 5‐carboxamidotryptamine (5‐CT; 5‐HT 1/7 and recombinant 5‐ht 5A/5B ), CP 93,129 ( r 5‐HT 1B ), sumatriptan (5‐HT 1B/1D ), PNU‐142633 (5‐HT 1D ) and ergotamine (5‐HT 1B/1D and recombinant 5‐ht 5A/5B ) mimicked the above sympatho‐inhibition to 5‐HT. In contrast, the agonists indorenate (5‐HT 1A ) and LY344864 (5‐ht 1F ) were inactive. Interestingly, 5‐CT‐induced cardiac sympatho‐inhibition was abolished by methiothepin, the cocktail of antagonists/inhibitors, GR 127935 or the combination of SB224289 (5‐HT 1B ) plus BRL15572 (5‐HT 1D ), but remained unchanged when SB224289 or BRL15572 were given separately. Therefore, 5‐HT‐induced cardiac sympatho‐inhibition, being unrelated to 5‐HT 2 , 5‐HT 3 , 5‐HT 4 , 5‐ht 6 , 5‐HT 7 receptors, α 1/2 ‐adrenoceptor or prostaglandin synthesis, seems to be primarily mediated by (i) 5‐HT 1 (probably 5‐HT 1B/1D ) receptors and (ii) a novel mechanism antagonized by methiothepin that, most likely, involves putative 5‐ht 5A/5B receptors.British Journal of Pharmacology (2003) 140 , 725–735. doi: 10.1038/sj.bjp.0705489