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-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).


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Arcuni
J C
JC
Department of Surgery, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Stoner
M C
MC
Kellum
J M
JM
D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D004338:Drug Combinations; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D000077526:Tropisetron; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology / Q000502:physiology*
D002712:Chlorides; D004338:Drug Combinations; D007211:Indoles; D010446:Peptide Fragments; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C113198:vasoactive intestinal peptide (6-28); D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D000077526:Tropisetron; C045918:2-methyl-5-HT