Vasoactive intestinal peptide is a neuropeptide mediator of the secretory response to serotonin in rat

Background. The chloride secretory response to serotonin (5-HT) has nonneural and neural mechanisms, the latter mediated through a 5-HT3 receptor. We hypothesized that 5-HT3-induced Cl- secretion is partially mediated by VIP as a neurosecretory transmitter. Therefore it should be inhibited by a VIP receptor antagonist, VIP 6-28. Furthermore, exogenous VIP should induce secretion in the presence of tetrodotoxin (TTX). Methods. Unstripped sheets of rat colon (n = 6) were mounted in Ussing chambers. The 5-HT3 receptor agonist 2-Me-5-HT (10 mu M) was added in the absence and presence of VIP 6-28 (30 mu M) in companion studies VIP (1 mu M) was added to tissue with or without TTX. Changes in short-circuit current (Delta I-sc) were recorded and repeat-measure ANOVA was used to analyze data. Results. Addition of 2-Me-5-HT induced a rise in Delta I-sc seen in controls at 1 to 5 min (3.2 +/- 1.5 to 12.3 +/- 3.7 mu A/cm(2), P < 0.02). VIP 6-28 blunted Delta I-sc (1.2 +/- 0.4 to 3.7 +/- 1.3 mu A/cm(2), P < 0.01). VIP caused Delta I-sc to increase above baseline in 15 min (4.7 +/- 2.6 to 10.4 +/- 3.0 mu A/cm(2), P < 0.01). The addition of TTX prior to VIP did not alter Delta I-sc. Conclusion. Activation of the neural 5-HT, receptor by 2-Me-5-HT induces a secretory response in rat colon that is inhibited by a VIP receptor antagonist. Exogenous VIP mimics this response and is unaffected by TTX. VIP is a likely nonadrenergic, noncholinergic neurotransmitter in this pathway. (C) 2000 Academic Press.