Involvement of the endogenous nitric oxide signalling system in bradykinin receptor activation in rat submandibular salivary gland.
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.
Genaro
A M
AM
Pharmacological Unit, School of Dentistry, Buenos Aires University - CONICET, Buenos Aires, Argentina.
Stranieri
G M
GM
Borda
E
E
D000704:Analysis of Variance; D000818:Animals; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
D018836:Inflammation Mediators; D010716:Phosphatidylinositols; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D006152:Cyclic GMP; D015232:Dinoprostone; D001920:Bradykinin