Bradykinin receptor-mediated chloride secretion in intestinal function

The nonapeptide bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) and the decapeptide kallidin (Lys-bradykinin) are released during tissue damage and cause vasodilation, increased vascular permeability, altered gut motility and pain^1-4. Accordingly, they have been implicated in several pathological processes, including carcinoid tumours and postgastrectomy dumping syndrome. Symptoms of these two syndromes include flushing, light-headedness, headaches and diarrhoea^5-9. Increased blood levels of bradykinin ^5,7-9 and kallikrein⁹, the bradykinin-releasing enzyme, have been noted in such patients and may explain these symptoms. However, while kinin-forming and -destroying activity has been noted in the gut ^10-14, bradykinin itself has not been directly demonstrated. Moreover, while bradykinin influences gut motility and electrical activity ^15,25,26, most clinical diarrhoea is due to ion and fluid secretion into the gut lumen rather than altered motility¹⁶. We describe here specific bradykinin receptors in intestinal mucosa and muscle. We also report that bradykinin and several peptide analogues potently stimulate chloride secretion in the gut with a peptide specificity indicative of specific receptor interactions. These findings suggest a physiological and a pathological role for kinins in intestinal function. Throughout this report the term kinin will indicate both bradykinin and kallidin activities since in several cases the true active form is unknown.