From:
Sukie Crandall
Date: 2008-01-15 18:05:39 UTC
Subject: [ferrethealth] abstract
To: ferrethealth@yahoogroups.com
Leads to future better GI approaches?
> J Pharmacol Exp Ther. 2008 Jan 11 [Epub ahead of print]
> Discovery and Characterization of Novel
>
> Tryptophan Hydroxylase Inhibitors That Selectively Inhibit Serotonin
> Synthesis in the Gastrointestinal Tract.
>
> Liu Q, Yang Q, Sun W, Vogel P, Heydorn W, Yu XQ, Hu Z, Yu A, Jonas
> B, Pineda R, Calderon-Gay V, Germann M, O'Neill E, Brommage
> R,Cullinan E, Platt KA, Wilson A, Powell DR, Sands AT, Zambrowicz
> BP,Shi ZC.
> Lexicon Pharmaceuticals, Inc.
>
> Serotonin (5-HT) is a neurotransmitter with both central and
> peripheral functions, including the modulation of mood, appetite,
> hemodynamics; and gastrointestinal (GI) sensation, secretion, and
> motility. Its synthesis is initiated by the enzyme tryptophan
> hydroxylase (TPH). Two isoforms of TPH have been discovered: TPH1,
> primarily expressed in the enterochromaffin cells of the
> gastrointestinal tract, and TPH2, expressed exclusively in neuronal
> cells. Mice lacking Tph1 contain little to no 5-HT in the blood and
> GI tract while maintaining normal levels in the brain. Since GI 5-HT
> is known to play important roles in normal and patho physiology, we
> set out to discover and characterize novel compounds that
> selectively inhibit biosynthesis of GI 5-HT. We describe here two of
> a series of these inhibitors that are potent for TPH activity both
> in biochemical and cell-based assays. This class of compounds has
> unique properties with respect to their pharmacokinetic and
> pharmacodynamic effects on GI serotonin production. Similar to the
> Tph1 knockout results, these TPH inhibitors have the ability to
> selectively reduce 5-HT levels in the murine GI tract without
> affecting brain 5-HT levels. In addition, administration of these
> compounds in a ferret model of chemotherapy-induced emesis caused
> modest reductions of intestinal serotonin levels as well as a
> decreased emetic response. These findings suggest that GI-specific
> TPH inhibitors may provide novel treatments for various
> gastrointestinal disorders associated with dysregulation of the GI
> serotonergic system, such as chemotherapy-induced emesis and
> irritable bowel syndrome (IBS).
> PMID: 18192499 [PubMed - as supplied by publisher]
>
>
Sukie (not a vet)
Recommended ferret health links:
http://pets.groups.yahoo.com/group/ferrethealth/
http://ferrethealth.org/archive/
http://www.afip.org/ferrets/index.html
http://www.miamiferret.org/fhc/
http://www.ferretcongress.org/
http://www.trifl.org/index.shtml
http://homepage.mac.com/sukie/sukiesferretlinks.html
Yahoo! Groups Links
<*> To visit your group on the web, go to:
http://groups.yahoo.com/group/ferrethealth/
<*> Your email settings:
Individual Email | Traditional
<*> To change settings online go to:
http://groups.yahoo.com/group/ferrethealth/join
(Yahoo! ID required)
<*> To change settings via email:
mailto:ferrethealth-digest@yahoogroups.com
mailto:ferrethealth-fullfeatured@yahoogroups.com
<*> To unsubscribe from this group, send an email to:
ferrethealth-unsubscribe@yahoogroups.com
<*> Your use of Yahoo! Groups is subject to:
http://docs.yahoo.com/info/terms/