Tachyphylaxis to 5-HT3-receptor-mediated activation of vagal afferents is prevented by co-activation of 5-HT2 receptors

• Published in: Brain research Vol. 1093; no. 1; pp. 105 - 115
• Main Authors: LACOLLEY, Patrick J, OWEN, Joy R, BATES, James N, JOHNSON, Alan Kim, LEWIS, Stephen J
• Format: Journal Article
• Language: English
• Published: London Elsevier 06.06.2006; Amsterdam; New York, NY
• Subjects: Animals; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Hemodynamics - drug effects; Hemodynamics - physiology; Male; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Serotonin, 5-HT2 - drug effects; Receptors, Serotonin, 5-HT2 - metabolism; Receptors, Serotonin, 5-HT3 - drug effects; Receptors, Serotonin, 5-HT3 - metabolism; Reflex - drug effects; Reflex - physiology; Serotonin Receptor Agonists - pharmacology; Tachyphylaxis - physiology; Vagus Nerve - drug effects; Vagus Nerve - metabolism; Vertebrates: nervous system and sense organs; Tachyphylaxis; Cardiovascular control; Rat; Serotonin; Vagal afferent; Rodentia; Activation; 5-HT2 Serotonine receptor; Heart rate; Vertebrata; Mammalia; Animal; 5-HT3 Serotonine receptor; Serotonin (5-HT); Neurotransmitter; Blood pressure; Hemodynamics; Vagus nerve; 5-HT3 receptor
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.03.090

Functional studies have provided evidence that 5-HT(3) ion-channel receptors (5-HT(3)Rs) on vagal cardiopulmonary afferents mediating the Bezold-Jarisch reflex (BJR) rapidly desensitize upon repeated exposure to selective 5-HT(3)R agonists. G-protein-coupled 5-HT(2) receptors (5-HT(2)Rs) also exist on vagal afferents, although activation of these receptors does not elicit the BJR. However, there is in vivo evidence that 5-HT(2)Rs may regulate the activity of 5-HT(3)Rs. The aim of this study was to determine whether co-activation of 5-HT(2)Rs prevents desensitization of 5-HT(3)Rs mediating the BJR in conscious rats. The principal findings were that (1) tachyphylaxis rapidly developed to the BJR-mediated hemodynamic responses elicited by successive injections of 5-HT(3)R agonists and (2) co-injection of the selective 5-HT(2)R agonist, alpha-methyl-5-HT, prevented tachyphylaxis to the BJR-mediated hemodynamic responses elicited by the 5-HT(3)R agonists. Additional studies provided evidence that (1) tachyphylaxis to the 5-HT(3)R agonists was not due to impairment of the central or efferent processing of the BJR, and (2) the pressor responses elicited by alpha-methyl-5-HT were not responsible for preventing tachyphylaxis to the BJR reflex responses elicited by 5-HT(3)R agonists. These results suggest that the loss of response to 5-HT(3)R agonists is due to desensitization of 5-HT(3)Rs on vagal afferents mediating the BJR and that co-activation of 5-HT(2)Rs prevents the desensitization of these 5-HT(3)Rs.