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Characterization of prejunctional 5‐HT receptors mediating inhibition of sympathetic vasopressor responses in the pithed rat
Author(s) -
Villalón Carlos M.,
Contreras Judith,
Juan Eduardo RamírezSan,
Castillo Carlos,
Perusquía Mercedes,
Terrón José A.
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.tb15143.x
Subject(s) - methysergide , ritanserin , endocrinology , medicine , ketanserin , metergoline , 5 ht receptor , tachyphylaxis , tropisetron , yohimbine , receptor antagonist , chemistry , stimulation , receptor , 5 ht1 receptor , inhibitory postsynaptic potential , desipramine , rauwolscine , prazosin , antagonist , serotonin , biology , antidepressant , hippocampus
1 It has recently been shown that continuous infusions of 5‐hydroxytryptamine (5‐HT) are able to inhibit, in a dose‐dependent manner, the pressor responses induced by preganglionic (T 7 ‐T 9 ) sympathetic stimulation in pithed rats pretreated with desipramine (50 μg kg −1 , i.v.). This inhibitory effect, besides being significantly more pronounced at lower frequencies of stimulation (0.03‐1 Hz) and devoid of tachyphylaxis, is reversible after interrupting the infusions of 5‐HT (up to 5.6 μg kg −1 min −1 ). In the present study we have characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5‐HT. 2 The inhibition induced by 5.6 μg kg −1 min −1 of 5‐HT on sympathetically‐induced pressor responses was not blocked after i.v. treatment with physiological saline (1 ml kg −1 ), ritanserin (0.1 mg kg −1 ), MDL 72222 (0.15 mg kg −1 ) or tropisetron (3 mg kg −1 ), which did not modify the sympathetically‐induced pressor responses per se , but was significantly antagonized by the 5‐HT 1 ‐like and 5‐HT 2 receptor antagonist, methysergide (0.3 mg kg −1 ), which also produced a slight attenuation of the pressor responses to 0.03 and 0.1 Hz per se . 3 Unexpectedly and contrasting with methysergide, the 5‐HT 1 ‐like and 5‐HT 2 receptor antagonists, methiothepin (0.01, 0.03 and 0.1 mg kg −1 ) and metergoline (1 and 3 mg kg −1 ), apparently failed to block the above 5‐HT‐induced inhibition. Nevertheless, it is noteworthy that these antagonists also blocked the electrically‐induced pressor responses per se , presumably by blockade of vascular α 1 ‐adrenoceptors and, indeed, this property might have masked their potential antagonism at the inhibitory 5‐HT 1 ‐like receptors. 4 Consistent with the above findings, 5‐carboxamidotryptamine (5‐CT, a potent 5‐HT 1 ‐like receptor agonist), metergoline and methysergide mimicked the inhibitory action of 5‐HT with the following rank order of agonist potency: 5CT> > 5‐HT > metergoline ≥ methysergide. 5 Taken together, the above results suggest that the inhibitory action of 5‐HT on the electrically‐induced pressor responses is primarily mediated by an action on inhibitory prejunctional 5‐HT 1 ‐like receptors leading to a decrease in the sympathetic nerve discharge. Interestingly, 5‐HT‐induced excitatory mechanisms could be made manifest once the inhibitory action of 5‐HT had been antagonized.