title: Peripheral 5-HT1A and 5-HT7 serotonergic receptors modulate parasympathetic neurotransmission in long-term diabetic rats.
abstract: We analyzed the modulation of serotonin on the bradycardia induced in vivo by vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT), effect reproduced by 5-carboxamidotryptamine maleate (5-CT), a 5-HT(1/7) agonist. The enhancement of the bradycardia at low doses of 5-CT was reproduced by 5-HT(1A) agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) and abolished by WAY-100,635, 5-HT(1A) antagonist. Pretreatment with 5-HT(1) antagonist methiothepin blocked the stimulatory and inhibitory effect of 5-CT, whereas pimozide, 5-HT(7) antagonist, only abolished 5-CT inhibitory action. In conclusion, long-term diabetes elicits changes in the subtype of the 5-HT receptor involved in modulation of vagally induced bradycardia. Activation of the 5-HT(1A) receptors induces enhancement, whereas attenuation is due to 5-HT(7) receptor activation. This 5-HT dual effect occurs at pre- and postjunctional levels.
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Restrepo
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martín
authors.forename: Luis
authors.initials: L
authors.lastname: San Román
authors.forename: Asunción
authors.initials: A
authors.lastname: Morán
mesh_terms: D000496:Alloxan; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism / Q000502:physiology*; D011985:Receptors, Serotonin / Q000378:metabolism / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D000496:Alloxan