title: Further evidence for the role of histamine H3, but not H1, H2 or H4, receptors in immepip-induced inhibition of the rat cardioaccelerator sympathetic outflow.
abstract: Since histamine H3 and H4 receptors are coupled to heterotrimeric Gi/o proteins, a signal transduction pathway associated with inhibition of neurotransmitter release, the present study has investigated the inhibition of the rat cardioaccelerator sympathetic outflow induced by the H3/H4 receptor agonist immepip by using antagonists for histamine H1 (ketotifen), H2 (ranitidine), H3 (thioperamide) and H4 (JNJ7777120) receptors. For this purpose, 102 male Wistar rats were pithed, artificially ventilated and prepared for either preganglionic spinal (C7-T1) stimulation of the cardioaccelerator sympathetic outflow (n=90) or i.v. bolus injections of noradrenaline (n=12). This approach resulted in frequency-dependent and dose-dependent tachycardic responses, respectively. I.v. continuous infusions of immepip (3 and 10 μg/kg min), but not of saline (0.02 ml/min), dose-dependently inhibited the sympathetically-induced tachycardic responses. Moreover, the cardiac sympatho-inhibition induced by 10 μg/kg min immepip (which failed to affect the tachycardic responses to i.v. noradrenaline) was: (i) unaltered after i.v. treatment with 1 ml/kg vehicle, 100 μg/kg ketotifen, 3000 μg/kg ranitidine, 30 μg/kg thioperamide or 300 μg/kg JNJ7777120; and (ii) abolished after 100 μg/kg thioperamide (i.v.). These doses of antagonists, which did not affect per se the sympathetically-induced tachycardic responses, were high enough to block their respective receptors. In conclusion, the cardiac sympatho-inhibition induced by 10 μg/kg.min immepip involves histamine H3 receptors, with further pharmacological evidence excluding the involvement of H1, H2 and H4 receptors.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios No. 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., México. Electronic address: manuelpinacho.unam@gmail.com.
authors.forename: Manuel
authors.initials: M
authors.lastname: Pinacho-García
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios No. 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., México. Electronic address: br.marichal@gmail.com.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Marichal-Cancino
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios No. 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., México. 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; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006633:Histamine Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D011968:Receptors, Histamine / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D000074040:Receptors, Histamine H4; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*
chemical_list: D006633:Histamine Antagonists; C498828:Hrh4 protein, rat; D007093:Imidazoles; D010880:Piperidines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D018100:Receptors, Histamine H3; D000074040:Receptors, Histamine H4; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D009638:Norepinephrine
keywords: Cardioaccelerator sympathetic outflow; Desipramine hydrochloride (Pubchem CID: 65327); Histamine receptors; Immepip; JNJ7777120 (Pubchem CID: 4908365); Pithed rat; gallamine triethiodide (Pubchem CID: 6172); immepip dihydrobromide (Pubchem CID: 16078980); ketotifen fumarate salt (Pubchem CID: 5282408); noradrenaline hydrochloride (Pubchem CID: 5923); ranitidine hydrochloride (Pubchem CID: 3033332); thioperamide maleate salt (Pubchem CID: 16220001)