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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

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

Manuel Pinacho-García, Bruno A Marichal-Cancino, Carlos M Villalón

Eur J Pharmacol. 2016 Feb 15;773:85-92.

PMID: 26826593

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	CAS Number	Price
AP148440817	Thioperamide maleate salt	148440-81-7	Price
AP164391473	Immepip dihydrobromide	164391-47-3	Price
AP34580148	Ketotifen fumarate salt	34580-14-8	Price

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