期刊
GASTROENTEROLOGY
卷 123, 期 5, 页码 1554-1564出版社
W B SAUNDERS CO
DOI: 10.1053/gast.2002.36581
关键词
-
资金
- NIDDK NIH HHS [R01 DK37238, R01 DK57075] Funding Source: Medline
Background & Aims: Serine proteases are postulated to influence gastrointestinal function by stimulating protease-activated receptors (PARS). This study identified the effects on myenteric neurons of activating PARs and investigated underlying mechanisms of action. Methods: Intracellular electrophysiologic methods were used to study the effects of proteases on electrical and synaptic behavior of morphologically identified neurons in the guinea pig enteric nervous system. Fluorescent immunohistochemistry was used to study the chemical coding of neurons that responded to PARs stimulation. Results: Application of thrombin, trypsin, or mast cell tryptase evoked slowly activating excitatory responses reminiscent of slow synaptic excitation in enteric neurons. Synthetic activating peptides for PAR-1, -2, and -4 receptors mimicked the actions of the proteases. The depolarizing responses evoked by PARS were insensitive to cyclooxygenase inhibitors and were suppressed by agents that inhibit phospholipase C (PLC) or block intraneuronal receptors for inositol triphosphate. A majority of PAR-sensitive uniaxonal neurons expressed immunoreactivity for nitric oxide synthase. Most of the PAR-sensitive AH Dogiel morphologic type II neurons were immunoreactive for calbindin. Conclusions: Excitatory responses to the serine proteases are mediated by PAR-1, -2, and -4 receptors. The mechanism of signal transduction involves stimulation of PLC and intraneuronal calcium mobilization and is independent of prostanoid formation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据