title: Peripheral 5-HT₁D and 5-HT₇ serotonergic receptors modulate sympathetic neurotransmission in chronic sarpogrelate treated rats.
abstract: 5-HT₂ receptor activation induces vasoconstriction, hypertension and platelet aggregation; therefore, its blocking may be useful in cardiovascular diseases, probably due to alterations in the modulation of serotonergic system. The aim of this study was to evaluate whether 5-HT₂ receptor blockade changes serotonergic modulation of sympathetic neurotransmission in pithed rats. Serotonergic modulation of sympathetic neurotransmission was investigated in Wistar rats treated with sarpogrelate, a 5-HT₂ receptor antagonist, during 14 days (30 mg/kg/day). After central nervous system destruction, we conducted electrical stimulation throughout the spinal cord flow to study the 5-HT-related products action on adrenergic system. 5-Hydroxytryptamine exerted inhibition of sympathetic outflow in sarpogrelate-treated pithed rats. This effect was mimicked and enhanced by 5-CT (5-HT₁/₇ receptor agonist). L-694,247 and AS-19, 5-HT₁D and 5-HT₇ receptor agonists respectively, reproduced this action. Pretreatment with LY310762+SB258719 (5-HT₁D and 5-HT₇ receptor antagonists, respectively) completely abolished 5-CT inhibitory action. The nature of this action was prejunctional since these agonists did not modify the pressor responses induced by exogenous noradrenaline. Western Blot analysis confirmed a higher expression of 5-HT₁D receptors in sarpogrelate-treated rats. Experimental 5-HT₂ receptor blockade induces changes in the 5-HT receptors involved in the serotonergic inhibition of sympathetic-induced pressor responses. Prejunctional activation of 5-HT₁D and 5-HT₇ receptors induces a significantly higher serotonergic inhibition on adrenergic neurotransmission in sarpogrelate-treated pithed rats. The antagonism of 5-HT₂ receptors produces an enhancement of serotonergic sympathoinhibitory effect, which may explain the beneficial effects of this blockade in cardiovascular disorders where 5-hydroxytryptamine plays a crucial role.
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain.
authors.forename: José Ángel
authors.initials: JÁ
authors.lastname: García-Pedraza
authors.forename: Mónica
authors.initials: M
authors.lastname: García
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martín
authors.forename: Jesús
authors.initials: J
authors.lastname: Gómez-Escudero
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodríguez-Barbero
authors.forename: Luis San
authors.initials: LS
authors.lastname: Román
authors.forename: Asunción
authors.initials: A
authors.lastname: Morán
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
chemical_list: D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013386:Succinates; C104425:serotonin 7 receptor; C064294:sarpogrelate; D009638:Norepinephrine
keywords: 5-CT; 5-HT; 5-HT(1D); 5-HT(2); 5-HT(7) receptors; Pithed rat; Prejunctional sympathoinhibition; Sarpogrelate