G protein-mediated dysfunction of excitation-contraction coupling in ileal inflammation

Xuan-Zheng Shi, Sushil K. Sarna

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Inflammation impairs the circular muscle contractile response to muscarinic (M) receptor activation. The aim of this study was to investigate whether the expression of muscarinic receptors, their binding affinity, and the expression and activation of receptor-coupled G proteins contribute to the suppression of contractility in inflammation. The studies were performed on freshly dissociated single smooth muscle cells from normal and inflamed canine ileum. Northern blotting indicated the presence of only M2 and M 3 receptors on canine ileal circular muscle cells. Inflammation did not alter the mRNA or protein expression of M2 and M3 receptors. The maximal binding and Kd values also did not differ between normal and inflamed cells. However, the contractile response to ACh in M3 receptor-protected cells was suppressed, whereas that in M 2 receptor-protected cells was enhanced. Further experiments indicated that the expression and binding activity of Gαq/11 protein, which couples to M3 receptors, were downregulated, whereas those of Gαi3, which couples to M2 receptors, were upregulated in inflamed cells. We concluded that inflammation depresses M 3 receptor function, but it enhances M2 receptor function in ileum. These effects are mediated by the differentially altered expression and binding activity of their respective coupled Gαq/11 and Gαi3 proteins.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume286
Issue number6 49-6
DOIs
StatePublished - Jun 2004

Fingerprint

Excitation Contraction Coupling
GTP-Binding Proteins
Inflammation
Muscarinic Receptors
Ileum
Canidae
Gq-G11 GTP-Binding Protein alpha Subunits
G-Protein-Coupled Receptors
Northern Blotting
Muscle Cells
Smooth Muscle Myocytes
Proteins
Down-Regulation
Muscles
Messenger RNA

Keywords

  • Acetylcholine
  • Inflammatory bowel disease
  • Motility
  • Signalopathy
  • Smooth muscle

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

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abstract = "Inflammation impairs the circular muscle contractile response to muscarinic (M) receptor activation. The aim of this study was to investigate whether the expression of muscarinic receptors, their binding affinity, and the expression and activation of receptor-coupled G proteins contribute to the suppression of contractility in inflammation. The studies were performed on freshly dissociated single smooth muscle cells from normal and inflamed canine ileum. Northern blotting indicated the presence of only M2 and M 3 receptors on canine ileal circular muscle cells. Inflammation did not alter the mRNA or protein expression of M2 and M3 receptors. The maximal binding and Kd values also did not differ between normal and inflamed cells. However, the contractile response to ACh in M3 receptor-protected cells was suppressed, whereas that in M 2 receptor-protected cells was enhanced. Further experiments indicated that the expression and binding activity of Gαq/11 protein, which couples to M3 receptors, were downregulated, whereas those of Gαi3, which couples to M2 receptors, were upregulated in inflamed cells. We concluded that inflammation depresses M 3 receptor function, but it enhances M2 receptor function in ileum. These effects are mediated by the differentially altered expression and binding activity of their respective coupled Gαq/11 and Gαi3 proteins.",
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AB - Inflammation impairs the circular muscle contractile response to muscarinic (M) receptor activation. The aim of this study was to investigate whether the expression of muscarinic receptors, their binding affinity, and the expression and activation of receptor-coupled G proteins contribute to the suppression of contractility in inflammation. The studies were performed on freshly dissociated single smooth muscle cells from normal and inflamed canine ileum. Northern blotting indicated the presence of only M2 and M 3 receptors on canine ileal circular muscle cells. Inflammation did not alter the mRNA or protein expression of M2 and M3 receptors. The maximal binding and Kd values also did not differ between normal and inflamed cells. However, the contractile response to ACh in M3 receptor-protected cells was suppressed, whereas that in M 2 receptor-protected cells was enhanced. Further experiments indicated that the expression and binding activity of Gαq/11 protein, which couples to M3 receptors, were downregulated, whereas those of Gαi3, which couples to M2 receptors, were upregulated in inflamed cells. We concluded that inflammation depresses M 3 receptor function, but it enhances M2 receptor function in ileum. These effects are mediated by the differentially altered expression and binding activity of their respective coupled Gαq/11 and Gαi3 proteins.

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