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

Biochemical signalling events coupled to the bradykinin Bz-receptor subtype , related to nitric oxide and prostaglandin E-2 generation were studied in rat submandibular gland. Bradykinin stimulation of the B-2-receptor trigger ed 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 oxi de synthase and cGMP production was blunted by agents able to interfere wit h 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, cG MP accumulation and prostaglandin E-2 generation. Furthermore, a specific i nhibitor of phospholipase A(2) blocked the bradykinin-induced prostaglandin E-2 release. These results suggest that apart, from the direct effect of b radykinin as an inducer of vasopermeability, it also appears to be a vasoac tive chemical mediator that triggers, through release of prostaglandin E-2, a feedback mechanism that induces a protective adaptation of the gland, mo dulating the course of inflammation. (C) 2000 Elsevier Science Ltd. All rig hts reserved.