Anion secretory effects of a non-peptide mimic of bradykinin (FR190997) onmouse colon epithelium

FR190997, a new non-peptide mimic was investigated using the chloride secre tory response of the mouse colon as a test system. The increase in short ci rcuit current (SCC) to FR190997 was approximately equal to that of lysyl br adykinin (LBK). It is shown that the current increase to FR190997 is due to electrogenic chloride secretion through an action at B-2-kinin receptors a nd involves prostaglandin formation. In these respects its actions are iden tical to those of LBK, except that the responses to FR190997 are prolonged. However FR190997 produces a long lasting desensitisation both to itself an d to LBK and it did not prove possible to protect against this using the hi gh affinity antagonist at B-2 receptors, Hoe 140. It is suggested that FR19 0997 either slows receptor recycling or leads to degradation of receptors, such that the reappearance of sensitivity may depend on new receptor synthe sis. (C) 1999 Elsevier Science B.V. All rights reserved.