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Pharmacological characterization of the new histamine H 4 receptor agonist VUF 8430
Author(s) -
Lim Herman D,
Adami Maristella,
Guaita Elena,
Werfel Thomas,
Smits Rogier A,
De Esch Iwan JP,
Bakker Remko A,
Gutzmer Ralf,
Coruzzi Gabriella,
Leurs Rob
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00200.x
Subject(s) - dimaprit , agonist , agmatine , histamine receptor , histamine , histamine h4 receptor , receptor , chemistry , histamine h1 receptor , histamine h2 receptor , histamine h3 receptor , medicine , pharmacology , endocrinology , biology , biochemistry , arginine , antagonist , amino acid
Background and purpose: We compare the pharmacological profiles of a new histamine H 4 receptor agonist 2‐(2‐guanidinoethyl)isothiourea (VUF 8430) with that of a previously described H 4 receptor agonist, 4‐methylhistamine. Experimental approach: Radioligand binding and functional assays were performed using histamine H 4 receptors expressed in mammalian cell lines. Compounds were also evaluated ex vivo in monocyte‐derived dendritic cells endogenously expressing H 4 receptors and in vivo in anaesthetized rats for gastric acid secretion activity. Key results: Both VUF 8430 and 4‐methylhistamine were full agonists at human H 4 receptors with lower affinity at rat and mouse H 4 receptors. Both compounds induced chemotaxis of monocyte‐derived dendritic cells. VUF 8430 also showed reasonable affinity and was a full agonist at the H 3 receptor. Agmatine is a metabolite of arginine, structurally related to VUF 8430, and was a H 4 receptor agonist with micromolar affinity. At histamine H 3 receptors, agmatine was a full agonist, whereas 4‐methylhistamine was an agonist only at high concentrations. Both VUF 8430 and agmatine were inactive at H 1 and H 2 receptors, whereas 4‐methylhistamine is as active as histamine at H 2 receptors. In vivo, VUF 8430 only caused a weak secretion of gastric acid mediated by H 2 receptors, whereas 4‐methylhistamine, dimaprit, histamine and amthamine, at equimolar doses, induced 2.5‐ to 6‐fold higher output than VUF 8430. Conclusions and implications: Our results suggest complementary use of 4‐methylhistamine and VUF 8430 as H 4 receptor agonists. Along with H 4 receptor antagonists, both agonists can serve as useful pharmacological tools in studies of histamine H 4 receptors.