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Characterization ofprejunctional 5‐HTreceptors mediatinginhibition ofsympatheticvasopressor responsesin the pithed rat Carlos M. VillalónJudith ContrerasEduardo Ramírez‐San Juan1995 год

Characterization of prejunctional 5‐HT receptors mediating inhibition of sympathetic vasopressor responses in the pithed rat
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Аннотация: 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 (T7-T9) 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-HT1-like and 5-HT2 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-HT1-like and 5-HT2 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 α1-adrenoceptors and, indeed, this property might have masked their potential antagonism at the inhibitory 5-HT1-like receptors. 4 Consistent with the above findings, 5-carboxamidotryptamine (5-CT, a potent 5-HT1-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-HT1-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.
Год издания: 1995
Авторы: Carlos M. Villalón, Judith Contreras, Eduardo Ramírez‐San Juan, Carlos Castillo, Mercedes Perusquı́a, José A. Terrón
Издательство: Wiley
Источник: British Journal of Pharmacology
Ключевые слова: Neurotransmitter Receptor Influence on Behavior, Neuroendocrine regulation and behavior, Receptor Mechanisms and Signaling
Другие ссылки: British Journal of Pharmacology (PDF)
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Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)