H₁‐Receptor activation triggers the endogenous nitric oxide signalling system in the rat submandibular gland

Abstract

BACKGROUND: Histamine is released from mast cells by immunologic and non-immunologic stimuli during salivary gland inflammation, regulating salivary secretion. The receptor-secretory mechanism has not been studied in detail. AIMS: The studies reported were directed toward elucidating signal transduction/second messenger pathways within the rat submandibular gland associated with 2-thiazolylethylamine (ThEA)-induced H(1)-receptor responses. MATERIALS AND METHODS: To assess the H(1) receptor subtype expression in the rat submandibular gland, a radioligand binding assay was performed. The study also included inositolphosphates and cyclic GMP accumulation, protein kinase C and nitric oxide synthase activities, and amylase release. RESULTS: The histamine H(1) receptor subtype is expressed on the rat submandibular gland with high-affinity binding sites. The ThEA effect was associated with activation of phosphoinositide-specific phospholipase C, translocation of protein kinase C, stimulation of nitric oxide synthase activity and increased production of cyclic GMP. ThEA stimulation of nitric oxide synthase and cyclic GMP was blunted by agents able to interfere with calcium movilization, while a protein kinase C inhibitor was able to stimulate ThEA action. On the other hand, ThEA stimulation evoked amylase release via the H1 receptor but was not followed by the L-arginine/nitric oxide pathway activation. CONCLUSIONS: These results suggest that, apart from the effect of ThEA on amylase release, it also appears to be a vasoactive chemical mediator that triggers vasodilatation, modulating the course of inflammation.

Protection of Radiation-Induced Damage to the Hematopoietic System, Small Intestine and Salivary Glands in Rats by JNJ7777120 Compound, a Histamine H4 Ligand

“…The presence of H 1 R and H 2 R in salivary glands was previously described [26]. In this study, we demonstrated the expression of H 4 R in some acinar and excretory ductal cells by immunohistochemistry, indicating that JNJ7777120 could be acting on H 4 R expressed in SMG.…”

Involvement of Nitric Oxide Synthase in the Mechanism of Histamine-Induced Inhibition of Leydig Cell Steroidogenesis via Histamine Receptor Subtypes in Sprague-Dawley Rats1

“…NO has been extensively demonstrated to inhibit steroid biosynthesis by reversibly binding to the heme group of cytochrome P450-dependent enzymes of the steroidogenic pathway [15,48,49]. There is evidence in the literature suggesting a role for intracellular NO as a mediator of HA actions in various nonsteroidogenic cell types [26][27][28]. We speculated that a similar situation might exist in Leydig cells and conducted a series of experiments to investigate this possibility.…”

“…Further studies [24,25] revealed the presence of a testis-specific variant of NOS1 (TnNOS) in human and mouse Leydig cells, in which it is encoded by the activity of a specific gene promoter. Of special interest, although NO can have a role as intracellular mediator of HA actions in various nonsteroidogenic cell types [26][27][28], the possibility that a similar situation might exist in Leydig cells has not been explored, to our knowledge.…”

Histamine modulates salivary secretion and diminishes the progression of periodontal disease in rat experimental periodontitis

“…Furthermore, previous studies have demonstrated the presence of histamine H1 and H2 receptor subtypes in rat SMG [31,48,49]. Histamine treatment also induces the translocation of aquaporin-5, which modulates water secretion to produce primary saliva, to the plasma membrane in human SMG cells through the histamine H1 receptor [31].…”