Jc. Arcuni et al., Vasoactive intestinal peptide is a neuropeptide mediator of the secretory response to serotonin in rat, J SURG RES, 91(2), 2000, pp. 118-122
Background. The chloride secretory response to serotonin (5-HT) has nonneur
al 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 sec
retion in the presence of tetrodotoxin (TTX).
Methods. Unstripped sheets of rat colon (n = 6) were mounted in Ussing cham
bers. The 5-HT3 receptor agonist 2-Me-5-HT (10 mu M) was added in the absen
ce 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 (Del
ta 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 control
s at 1 to 5 min (3.2 +/- 1.5 to 12.3 +/- 3.7 mu A/cm(2), P < 0.02). VIP 6-2
8 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 a
lter 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 antagon
ist. Exogenous VIP mimics this response and is unaffected by TTX. VIP is a
likely nonadrenergic, noncholinergic neurotransmitter in this pathway. (C)
2000 Academic Press.