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

Abstract 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.