title: Pharmacological evidence that histamine H3 receptors inhibit the vasodepressor responses by selective stimulation of the rat perivascular sensory CGRPergic outflow.
abstract: This study has investigated whether pharmacological activation of Gi/o coupled histamine H3/H4 receptors inhibits the rat vasodepressor sensory outflow. For this purpose, 100 male Wistar rats were pithed, artificially ventilated and pretreated (i.v.) with: 25mg/kg gallamine, 2mg/kg/min hexamethonium and 20μg/kg/min methoxamine, followed by i.v. continuous infusions of physiological saline (0.02ml/min) or immepip (3.1, 10 or 31μg/kg/min; a histamine H3/H4 receptor agonist). Under these conditions, electrical stimulation (0.56-5.6Hz; 50V and 2ms) of the spinal cord (T9-T12) resulted in frequency-dependent vasodepressor responses, which were: (i) unchanged during the infusions of saline or immepip (3.1μg/kg/min); and (ii) significantly but, surprisingly, not dose-dependently inhibited by 10 and 31μg/kg/min immepip. Moreover, the sensory-inhibition by 10μg/kg/min immepip (which failed to inhibit the vasodepressor responses by i.v. bolus injections of α-CGRP; 0.1-1µg/kg) was: (i) essentially unaltered after i.v. administration of saline (1ml/kg) or blocking doses of the antagonists ketotifen (100μg/kg; H1), ranitidine (1000μg/kg; H2) or JNJ7777120 (310μg/kg; H4); and (ii) abolished after i.v. thioperamide (310µg/kg; H3). In conclusion, our results suggest that immepip-induced inhibition of the vasodepressor sensory outflow is mainly mediated by prejunctional activation of histamine H3 receptors.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. Tenorios No. 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., Mexico. Electronic address: manriquegpe@yahoo.com.mx.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Manrique-Maldonado
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. Tenorios No. 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., Mexico. Electronic address: alhaales@gmail.com.
authors.forename: Alain H
authors.initials: AH
authors.lastname: Altamirano-Espinoza
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. Tenorios No. 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., Mexico. Electronic address: wachax@gmail.com.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Marichal-Cancino
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. Tenorios No. 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., Mexico. Electronic address: e.r.m_89@hotmail.com.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rivera-Mancilla
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. Tenorios No. 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., Mexico. Electronic address: vectoraviles@gmail.com.
authors.forename: Victor
authors.initials: V
authors.lastname: Avilés-Rosas
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. Tenorios No. 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., Mexico. Electronic address: cvillalon@cinvestav.mx.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D018100:Receptors, Histamine H3 / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
chemical_list: D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D010880:Piperidines; D018100:Receptors, Histamine H3; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; C052075:thioperamide; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; Gallamine triethiodide (Pubchem CID: 6172); Hexamethonium chloride (Pubchem CID: 93550); Histamine receptors; Immepip dihydrobromide (Pubchem CID: 16078980); JNJ7777120 (Pubchem CID: 4908365); Ketotifen fumarate salt (Pubchem CID: 5282408); Methoxamine hydrochloride (Pubchem CID: 6081); Pithed rat; Ranitidine hydrochloride (Pubchem CID: 3033332); Sensory CGRPergic outflow; Thioperamide maleate salt (Pubchem CID: 16220001); α-CGRP (Pubchem CID: 56841902)