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: Beatriz Restrepo, María Luisa Martín, Luis San Román, Asunción Morán
• Journal: Experimental diabetes research (Exp Diabetes Res) Vol. 2010 Pg. 686734 ( 2010) ISSN: 1687-5303 [Electronic] United States
• PMID: 21403818 (Publication Type: Journal Article)

Chemical References

• Receptors, Serotonin
• Serotonin Antagonists
• Serotonin Receptor Agonists
• serotonin 7 receptor
• Receptor, Serotonin, 5-HT1A
• Serotonin
• Alloxan

Topics

• Alloxan
• Animals
• Blood Pressure (drug effects, physiology)
• Bradycardia (etiology, metabolism, physiopathology)
• Diabetes Mellitus, Experimental (chemically induced, complications, metabolism, physiopathology)
• Diabetic Cardiomyopathies (etiology, metabolism, pathology)
• Hemodynamics
• Male
• Parasympathetic Nervous System (drug effects, metabolism, physiology)
• Rats
• Rats, Wistar
• Receptor, Serotonin, 5-HT1A (metabolism, physiology)
• Receptors, Serotonin (metabolism, physiology)
• Serotonin (pharmacology)
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Synaptic Transmission (drug effects, physiology)
• Time Factors