Abstract
We report the establishment of a new model for measuring gastric tone and liquid meal-induced accommodation in conscious guinea pigs and the role played by transient receptor potential ankyrin 1 (TRPA1). An indwelling polyethylene bag was placed in proximal stomachs of 5-week-old male Hartley guinea pigs. Gastric tone was measured by distending the bag and recording changes in intrabag pressure at various volumes. Gastric accommodation was measured by administering liquid meals and recording intrabag pressure over time. Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) (a nitric-oxide synthase inhibitor), atropine sulfate (atropine) (a muscarinic receptor antagonist), allyl isothiocyanate (AITC) (a TRPA1 agonist), or theophylline-7-(N-4-isopropylphenyl) acetamide (HC-030031) (a selective TRPA1 antagonist) was administered 15 to 60 min before measurement. Gastric tone was increased by stepwise distension of the bag and was further significantly increased by l-NAME and significantly decreased by atropine. A liquid meal (15% w/v; 1.7 kcal) significantly decreased intrabag pressure 5 to 20 min after administration, indicating gastric accommodation; this was completely suppressed by l-NAME and further enhanced by atropine. AITC significantly increased gastric tone; this increase was decreased by HC-030031 and atropine. A combination of AITC and l-NAME significantly increased gastric tone compared with l-NAME alone. HC-030031 alone significantly decreased gastric tone. Liquid meal-induced gastric accommodation was significantly suppressed by pretreatment with AITC. We established a new model for measuring gastric tone and accommodation in conscious guinea pigs. TRPA1 activation suppresses gastric accommodation by increasing gastric tone through cholinergic neuronal pathways.
Footnotes
H.M. was supported by grants from Tsumura & Co. from 2006 to 2011.
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.
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ABBREVIATIONS:
- TRPA1
- transient receptor potential ankyrin 1
- l-NAME
- Nω-nitro-l-arginine methyl ester hydrochloride
- AITC
- allyl isothiocyanate
- HC-030031
- theophylline-7-(N-4-isopropylphenyl) acetamide
- TRPV1
- transient receptor potential vanilloid receptor 1
- NO
- nitric oxide
- LM
- liquid meal.
- Received October 17, 2011.
- Accepted January 17, 2012.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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