NEUROKININ-A INCREASES DUODENAL MUCOSAL PERMEABILITY, BICARBONATE SECRETION, AND FLUID OUTPUT IN THE RAT

The aim of this study was to examine the integrative response to neuro kinin A (NKA) on duodenal mucosal permeability, bicarbonate secretion, fluid flux, and motility in an in situ perfusion model in anesthetize d rats. Intravenous infusion of NKA. (100, 200, and 400 pmol.kg(-1).mi n(-1)) induced duodenal motility. Furthermore, duodenal mucosal bicarb onate secretion, fluid output, and mucosal permeability increased in r esponse to NKA. Pretreatment with the nicotinic antagonist hexamethoni um did not change the response in any of the parameters investigated, whereas the NK2-receptor antagonist MEN 10,627 effectively inhibited a ll responses to NKA. Indomethacin induced duodenal motility and stimul ated bicarbonate secretion. In indomethacin-treated rats, NKA further increased motility but decreased indomethacin-stimulated bicarbonate s ecretion by 70%. The NKA-induced increase in mucosal permeability was unaltered by indomethacin. It is concluded that NKA not only induces m otility but also increases mucosal permeability and fluid output. Furt hermore, the neuropeptide may have both stimulative and inhibitory eff ects on bicarbonate secretion. All responses to NKA. are dependent on NK-2 receptor activation but are not mediated through nicotinic recept ors.