Involvement of the endogenous nitric oxide signalling system in bradykinin receptor activation in rat submandibular salivary gland

• Published in: Archives of oral biology 2000-09, Vol.45 (9), p.723-729
• Main Authors: Genaro, Ana M., Stranieri, Graciela M., Borda, Enri
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Bradykinin; Bradykinin - metabolism; Bradykinin - pharmacology; cGMP; Cyclic GMP - biosynthesis; Dentistry; Dinoprostone - biosynthesis; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Inflammation Mediators - metabolism; Male; Nitric Oxide - biosynthesis; Nitric oxide synthase; Nitric Oxide Synthase - metabolism; Phosphatidylinositols - metabolism; Phosphoinositide turnover; Prostaglandin E 2; Protein kinase C; Protein Kinase C - metabolism; Rats; Rats, Wistar; Receptor, Bradykinin B2; Receptors, Bradykinin - agonists; Receptors, Bradykinin - metabolism; Salivary gland; Signal Transduction - physiology; Statistics, Nonparametric; Submandibular Gland - drug effects; Submandibular Gland - metabolism; Vasodilator Agents - pharmacology
• ISSN: 0003-9969; 1879-1506
• DOI: 10.1016/S0003-9969(00)00048-0

Biochemical signalling events coupled to the bradykinin B 2-receptor subtype, related to nitric oxide and prostaglandin E 2 generation were studied in rat submandibular gland. Bradykinin stimulation of the B 2-receptor triggered activation of phosphoinositide turnover, translocation of protein kinase C, stimulation of nitric oxide synthase activity, increased production of cGMP and release of prostaglandin E 2. Bradykinin stimulation of nitric oxide synthase and cGMP production was blunted by agents able to interfere with calcium/calmodulin and phospholipase C activities, while a protein kinase C inhibitor was able to stimulate bradykinin action. Moreover, a specific B 2-bradykinin antagonist of the reversible nitric oxide synthase inhibitor abrogated the bradykinin stimulation of nitric oxide synthase activity, cGMP accumulation and prostaglandin E 2 generation. Furthermore, a specific inhibitor of phospholipase A 2 blocked the bradykinin-induced prostaglandin E 2 release. These results suggest that apart, from the direct effect of bradykinin as an inducer of vasopermeability, it also appears to be a vasoactive chemical mediator that triggers, through release of prostaglandin E 2, a feedback mechanism that induces a protective adaptation of the gland, modulating the course of inflammation.