Vasoactive intestinal peptide is a neuropeptide mediator of the secretory response to serotonin in rat. 2000

J C Arcuni, and M C Stoner, and J M Kellum
Department of Surgery, Virginia Commonwealth University, Richmond, Virginia 23298, USA.

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.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008297 Male Males
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D002712 Chlorides Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D000077526 Tropisetron An indole derivative and 5-HT3 RECEPTOR antagonist that is used for the prevention of nausea and vomiting. (3 alpha-Tropanyl)-1H-indole-3-carboxylic Acid Ester,ICS 205-930,ICS-205-930,ICS-205930,Indole-3-carboxylic Acid Tropine Ester,Navoban,Tropisetron Hydrochloride,ICS 205 930,ICS 205930,Indole 3 carboxylic Acid Tropine Ester
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D012702 Serotonin Antagonists Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS. 5-HT Antagonist,5-HT Antagonists,5-Hydroxytryptamine Antagonist,5-Hydroxytryptamine Antagonists,Antiserotonergic Agent,Antiserotonergic Agents,Serotonin Antagonist,Serotonin Blockader,Serotonin Blockaders,Serotonin Receptor Antagonist,Serotonin Receptor Blocker,Antagonists, 5-HT,Antagonists, 5-Hydroxytryptamine,Antagonists, Serotonin,Serotonin Receptor Antagonists,Serotonin Receptor Blockers,5 HT Antagonist,5 HT Antagonists,5 Hydroxytryptamine Antagonist,5 Hydroxytryptamine Antagonists,Agent, Antiserotonergic,Agents, Antiserotonergic,Antagonist, 5-HT,Antagonist, 5-Hydroxytryptamine,Antagonist, Serotonin,Antagonist, Serotonin Receptor,Antagonists, 5 HT,Antagonists, 5 Hydroxytryptamine,Antagonists, Serotonin Receptor,Blockader, Serotonin,Blockaders, Serotonin,Blocker, Serotonin Receptor,Blockers, Serotonin Receptor,Receptor Antagonist, Serotonin,Receptor Antagonists, Serotonin,Receptor Blocker, Serotonin,Receptor Blockers, Serotonin

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