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Pharmacological Evidence That Histamine H3 Receptors Inhibit the Vasodepressor Responses by Selective Stimulation of the Rat Perivascular Sensory CGRPergic Outflow

Pharmacological Evidence That Histamine H3 Receptors Inhibit the Vasodepressor Responses by Selective Stimulation of the Rat Perivascular Sensory CGRPergic Outflow

Guadalupe Manrique-Maldonado, Alain H Altamirano-Espinoza, Bruno A Marichal-Cancino, Eduardo Rivera-Mancilla, Victor Avilés-Rosas, Carlos M Villalón

Eur J Pharmacol. 2015 May 5;754:25-31.

PMID: 25704614

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.

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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