H(1)-Receptor activation triggers the endogenous nitric oxide signalling system in the rat submandibular gland.
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.


OBJECTIVE
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.


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.
Borda
Enri
E
Pharmacology Unit, School of Dentistry and Pharmacology Department, School of Medicine, University of Buenos Aires and National Research Council of Argentina (CONICET), Buenos Aires, Argentina. enri@farmaco.odon.uba.ar
Stranieri
Graciela
G
Sterin-Borda
Leonor
L
D000681:Amylases / Q000378:metabolism; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D017442:Histamine Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011969:Receptors, Histamine H1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013363:Submandibular Gland / Q000187:drug effects / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D017442:Histamine Agonists; D010716:Phosphatidylinositols; D011969:Receptors, Histamine H1; D013844:Thiazoles; C029345:2-(2-aminoethyl)thiazole; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010738:Type C Phospholipases; D000681:Amylases; D006152:Cyclic GMP