The D2/D3 agonist PD128907 (R-(+)-trans-3,4a,10b-tetrahydro-4-Propyl-2H,5H- [1]benzopyrano[4,3-b]-1,4-oxazin-9-ol) inhibits stimulated pyloric relaxation and spontaneous gastric emptying

Purna Kashyap, Maria Micci, Sarina Pasricha, Pankaj Jay Pasricha

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background Enteric neuronal dopamine (DA) inhibits acetylcholine release and gastric motility; this has been thought to be mediated via neuronal dopamine-2 receptor (D2R). The aim of this study was to investigate the modulation of gastric motility by the dopamine-3 receptor (D3R). Methods Adult Sprague-Dawley rats were used. Pyloric relaxation in response to electrical field stimulation (EFS) was assessed in an organ bath in the presence of varying concentrations of a selective D3R agonist, PD128907. Gastric emptying was assessed by the phenol red method after rats were treated with varying doses of PD128907 or DA with and without a selective D3R antagonist, l-nafadotride. Results Immunoblotting and immunohistochemistry confirmed the presence of D3R in the myenteric neurons in the rat pylorus. D3R activation reduced EFS-induced relaxation of pyloric strips in a dose-dependent manner and significantly delayed gastric emptying compared with vehicle. The D3R antagonist partially reversed the effect of DA on gastric emptying. Conclusions Our data suggest a novel role for D3R in regulation of gastric motility. D3R activation delays gastric emptying, an effect that may be due to impairment of pyloric relaxation. D3R antagonists therefore hold promise as useful agents for treatment of gastric motility disorders.

Original languageEnglish (US)
Pages (from-to)57-62
Number of pages6
JournalDigestive Diseases and Sciences
Volume54
Issue number1
DOIs
StatePublished - Jan 2009

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Gastric Emptying
Dopamine Receptors
Dopamine Antagonists
Dopamine
Stomach
Electric Stimulation
Phenolsulfonphthalein
Gastrointestinal Agents
Pylorus
Dopamine Agonists
Baths
Immunoblotting
Acetylcholine
Sprague Dawley Rats
3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol
Immunohistochemistry
Neurons

Keywords

  • Dopamine 3 receptor
  • Gastric emptying
  • Rat
  • Stomach

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

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title = "The D2/D3 agonist PD128907 (R-(+)-trans-3,4a,10b-tetrahydro-4-Propyl-2H,5H- [1]benzopyrano[4,3-b]-1,4-oxazin-9-ol) inhibits stimulated pyloric relaxation and spontaneous gastric emptying",
abstract = "Background Enteric neuronal dopamine (DA) inhibits acetylcholine release and gastric motility; this has been thought to be mediated via neuronal dopamine-2 receptor (D2R). The aim of this study was to investigate the modulation of gastric motility by the dopamine-3 receptor (D3R). Methods Adult Sprague-Dawley rats were used. Pyloric relaxation in response to electrical field stimulation (EFS) was assessed in an organ bath in the presence of varying concentrations of a selective D3R agonist, PD128907. Gastric emptying was assessed by the phenol red method after rats were treated with varying doses of PD128907 or DA with and without a selective D3R antagonist, l-nafadotride. Results Immunoblotting and immunohistochemistry confirmed the presence of D3R in the myenteric neurons in the rat pylorus. D3R activation reduced EFS-induced relaxation of pyloric strips in a dose-dependent manner and significantly delayed gastric emptying compared with vehicle. The D3R antagonist partially reversed the effect of DA on gastric emptying. Conclusions Our data suggest a novel role for D3R in regulation of gastric motility. D3R activation delays gastric emptying, an effect that may be due to impairment of pyloric relaxation. D3R antagonists therefore hold promise as useful agents for treatment of gastric motility disorders.",
keywords = "Dopamine 3 receptor, Gastric emptying, Rat, Stomach",
author = "Purna Kashyap and Maria Micci and Sarina Pasricha and Pasricha, {Pankaj Jay}",
year = "2009",
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doi = "10.1007/s10620-008-0335-6",
language = "English (US)",
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pages = "57--62",
journal = "Digestive Diseases and Sciences",
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T1 - The D2/D3 agonist PD128907 (R-(+)-trans-3,4a,10b-tetrahydro-4-Propyl-2H,5H- [1]benzopyrano[4,3-b]-1,4-oxazin-9-ol) inhibits stimulated pyloric relaxation and spontaneous gastric emptying

AU - Kashyap, Purna

AU - Micci, Maria

AU - Pasricha, Sarina

AU - Pasricha, Pankaj Jay

PY - 2009/1

Y1 - 2009/1

N2 - Background Enteric neuronal dopamine (DA) inhibits acetylcholine release and gastric motility; this has been thought to be mediated via neuronal dopamine-2 receptor (D2R). The aim of this study was to investigate the modulation of gastric motility by the dopamine-3 receptor (D3R). Methods Adult Sprague-Dawley rats were used. Pyloric relaxation in response to electrical field stimulation (EFS) was assessed in an organ bath in the presence of varying concentrations of a selective D3R agonist, PD128907. Gastric emptying was assessed by the phenol red method after rats were treated with varying doses of PD128907 or DA with and without a selective D3R antagonist, l-nafadotride. Results Immunoblotting and immunohistochemistry confirmed the presence of D3R in the myenteric neurons in the rat pylorus. D3R activation reduced EFS-induced relaxation of pyloric strips in a dose-dependent manner and significantly delayed gastric emptying compared with vehicle. The D3R antagonist partially reversed the effect of DA on gastric emptying. Conclusions Our data suggest a novel role for D3R in regulation of gastric motility. D3R activation delays gastric emptying, an effect that may be due to impairment of pyloric relaxation. D3R antagonists therefore hold promise as useful agents for treatment of gastric motility disorders.

AB - Background Enteric neuronal dopamine (DA) inhibits acetylcholine release and gastric motility; this has been thought to be mediated via neuronal dopamine-2 receptor (D2R). The aim of this study was to investigate the modulation of gastric motility by the dopamine-3 receptor (D3R). Methods Adult Sprague-Dawley rats were used. Pyloric relaxation in response to electrical field stimulation (EFS) was assessed in an organ bath in the presence of varying concentrations of a selective D3R agonist, PD128907. Gastric emptying was assessed by the phenol red method after rats were treated with varying doses of PD128907 or DA with and without a selective D3R antagonist, l-nafadotride. Results Immunoblotting and immunohistochemistry confirmed the presence of D3R in the myenteric neurons in the rat pylorus. D3R activation reduced EFS-induced relaxation of pyloric strips in a dose-dependent manner and significantly delayed gastric emptying compared with vehicle. The D3R antagonist partially reversed the effect of DA on gastric emptying. Conclusions Our data suggest a novel role for D3R in regulation of gastric motility. D3R activation delays gastric emptying, an effect that may be due to impairment of pyloric relaxation. D3R antagonists therefore hold promise as useful agents for treatment of gastric motility disorders.

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