TACHYKININS MEDIATE CHANGES IN ION-TRANSPORT IN PORCINE JEJUNUM THROUGH RELEASE OF PROSTAGLANDINS AND NEUROTRANSMITTERS

In the present study, we investigated the mediators involved in substa nce P (SP) and neurokinin A (NKA) induced ion transport. Stripped prep arations of porcine jejunal tissue were mounted in Ussing-chambers and short-circuited, The cyclo-oxygenase inhibitor, piroxicam (10 mu M) a nd the neuronal conduction blocker, tetrodotoxin (TTX) (0.1 mu M) both significantly decreased the SP (0.1 mu M) (66% and 36%, respectively) and NKA (1 mu M) (64% and 31%, respectively) induced increase in shor t-circuit current (SCC). Pretreatment with both piroxicam and TTX tota lly abolished the SP and NKA response. SP (0.1 mu M) caused a signific ant release of prostaglandin E-2 (PGE(2)), whereas the release of PGE( 2) induced by NKA was not significant. Experiments were performed to c larify if vasoactive intestinal polypeptide (VIP) was mediating SP or NKA responses. VIP caused a TTX-insensitive and a concentration-depend ent increase in SCC. Two VIP antagonists did not change the response t o VIP (10 nM and 0.1 mu M). Thus, these antagonists could not be used to further elucidate the role of VIP. We were unable to measure a sign ificant release of VIP after SP or NKA treatment. These results indica te, that SP and NKA regulate ion transport in porcine jejunum, entirel y through the release of prostaglandins and enteric neurotransmitters. (C) 1998 Published by Elsevier Science B.V All rights reserved.