Neurokinin A increases short-circuit current across rat colonic mucosa: a role for vasoactive intestinal polypeptide.

1. Neurokinin A (NKA) is a mammalian tachykinin distributed principally in the nervous system, including the myenteric innervation of the gut. 2. NKA may be involved in neurogenic inflammation and as a modulatory factor in the diarrhoea associated with mucosal inflammation of inflammatory bowel disease (ulcerative colitis). 3. We evaluated the effect of NKA on the short-circuit current ISC, assumed to reflect electrogenic chloride secretion, across muscle-stripped rat colonic mucosa mounted in Ussing chambers. 4. Serosal addition of NKA produced a concentration-dependent (0.1-100 nM) increase in ISC with an EC50 (half-maximal effective concentration) value of 7.5 nM. The maximum (mean +/- S.E.M.) increase in ISC (microA/cm2) for NKA was 111 +/- 10. 5. Tetrodotoxin (0.5 microM) and bumetanide (10 microM), but not atropine (1.0 microM), hexamethonium (100 microM) or pyrilamine (10 microM), significantly inhibited NKA-induced increases in ISC. 6. The response to NKA was attenuated by 45 min pre-treatment with antisera raised against vasoactive intestinal polypeptide (VIP). Moreover, prior desensitization to VIP attenuated the effect of NKA. 7. These studies suggest that NKA increases ISC in rat colon, in part, through a non-cholinergic neural mechanism involving VIP.