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

Biochemical signalling events coupled to the bradykinin B2-receptor subtype, related to nitric oxide and prostaglandin E2 generation were studied in rat submandibular gland. Bradykinin stimulation of the B2-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 E2. 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 B2-bradykinin antagonist of the reversible nitric oxide synthase inhibitor abrogated the bradykinin stimulation of nitric oxide synthase activity, cGMP accumulation and prostaglandin E2 generation. Furthermore, a specific inhibitor of phospholipase A2 blocked the bradykinin-induced prostaglandin E2 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 E2, a feedback mechanism that induces a protective adaptation of the gland, modulating the course of inflammation.