The intradermal effects of the H₃ receptor agonist R α methylhistamine in human skin

Abstract

We have investigated the possible existence of the H3 histamine receptor in human skin with the highly selective ligands R alpha methylhistamine (RAMHA) (H3 agonist) and thioperamide (H3 antagonist). We compared the intradermal effects of RAMHA with histamine, and studied their potential modulation by the H1 antagonist terfenadine, and H2 antagonist cimetidine. The effects of RAMHA and thioperamide on codeine phosphate-, substance P- and histamine-induced weal and flare responses were also studied. RAMHA produced dose-related weal and flare responses that were approximately 10- and fivefold less, respectively, than responses to histamine. Flare responses to RAMHA were significantly inhibited by oral terfenadine (P < 0.05). Weal and flare responses to histamine after oral cimetidine showed much intersubject variation, and cimetidine did not significantly alter either RAMHA- or histamine-induced weal and flare responses. Codeine phosphate-, substance P- and histamine-induced responses were not significantly affected by concurrent administration of RAMHA. Thioperamide was not found to influence codeine phosphate-, substance P-, RAMHA- or histamine-induced effects. RAMHA induces vascular (weal and flare) responses in human skin, and these responses are partially inhibited by terfenadine. There is a trend for RAMHA to have an additive effect to the weal induced by substance P and histamine, although our results largely do not reach statistical significance. Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate, histamine or substance P. We cannot conclude that the effects of RAMHA are induced by H3 receptors on cutaneous endothelial or mast cells.

Effect of combined histamine H1 and H3 receptor blockade on cutaneous microvascular permeability elicited by compound 48/80

“…These investigators concluded that H 3 receptors do not appear to inhibit histamine release in human skin. Consistent with the observations of Kavannagh et al (1998) we presently show that thioperamide or clobenpropit given alone at doses that block H 3 receptors in vivo does not alter the cutaneous microvascular permeability responses elicited by compound 48/80 (McLeod et al, 1996(McLeod et al, , 1999. However, when histamine H 1 receptors were blocked with chlorpheniramine, we demonstrate a significant H 3 component contributing to the extravasation of Evans blue evoked by compound 48/80.…”

“…Kavannagh et al (1998) showed that i.d. Ra-methylhistamine, an H 3 agonist, produces wheal and flare responses in human skin.…”

Understanding Pruritus in Systemic Disease

“…6 Recently described histamine H3 receptors behave as autoreceptors regulating release and biosynthesis of histamine in the central nerous system (CNS) and other tissues, including skin. 7,8 The H3 receptors may also form a link with other receptor systems, making the whole picture even more confusing. 9 The majority of histamine released in the skin originates from the dermal mast cells.…”

Dry environment increases mast cell number and histamine content in dermis in hairless mice

“…The existence and the role of the histamine H 3 receptor in skin is still unclear in humans 22 . However, in rats, the histamine H 3 receptor on mast cells is involved in the inhibitory effect on histamine release, 23 and the regulation of substance P release is also mediated via prejunctional histamine H 3 receptors located on peripheral endings of sensory nerves 24 .…”