Arcuni J C, Stoner M C, Kellum J M
Department of Surgery, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
J Surg Res. 2000 Jun 15;91(2):118-22. doi: 10.1006/jsre.2000.5915.
The chloride secretory response to serotonin (5-HT) has nonneural and neural mechanisms, the latter mediated through a 5-HT(3) receptor. We hypothesized that 5-HT(3)-induced C1(-) 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).
Unstripped sheets of rat colon (n = 6) were mounted in Ussing chambers. The 5-HT(3) receptor agonist 2-Me-5-HT (10 microM) was added in the absence and presence of VIP 6-28 (30 microM). In companion studies VIP (1 microM) was added to tissue with or without TTX. Changes in short-circuit current (DeltaI(SC)) were recorded and repeat-measure ANOVA was used to analyze data.
Addition of 2-Me-5-HT induced a rise in DeltaI(SC) seen in controls at 1 to 5 min (3.2 +/- 1.5 to 12.3 +/- 3.7 microA/cm(2), P < 0.02). VIP 6-28 blunted DeltaI(SC) (1.2 +/- 0.4 to 3.7 +/- 1.3 microA/cm(2), P < 0.01). VIP caused DeltaI(SC) to increase above baseline in 15 min (4.7 +/- 2.6 to 10.4 +/- 3.0 microA/cm(2), P < 0.01). The addition of TTX prior to VIP did not alter DeltaI(SC).
Activation of the neural 5-HT(3) 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.
