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

详细信息    查看全文

• 作者：Manuel Pinacho-Garcí ; a ^{manuelpinacho.unam@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Bruno A. Marichal-Cancino ^{br.marichal@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Carlos M. Villaló ; n ; ¹ ; ^{cvillalon@cinvestav.mx" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Desipramine hydrochloride (Pubchem CID ; 65327) ; gallamine triethiodide (Pubchem CID ; 6172) ; immepip dihydrobromide (Pubchem CID ; 16078980) ; JNJ7777120 (Pubchem CID ; 4908365) ; ketotifen fumarate salt (Pubchem CID ; 5282408) ; noradrenaline hydrochloride (Pubchem CID ; 5923) ; ranitidine hydrochloride (Pubchem CID ; 3033332) ; thioperamide maleate salt (Pubchem CID ; 16220001)
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 February 2016
• 年：2016
• 卷：773
• 期：Complete
• 页码：85-92
• 全文大小：531 K

文摘

Since histamine H₃ and H₄ receptors are coupled to heterotrimeric G_i/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.