Ca 2+ -induced contraction of cat esophageal circular smooth muscle cells

Cao, W.; Chen, Q.; Sohn, U. D.; Kim, N.; Kirber, M. T.; Harnett, K. M.; Behar, J.; Biancani, P.

doi:10.1152/ajpcell.2001.280.4.c980

Cited by 28Protein Kinase Regulation and GTPase SignalingIon channel regulation and functionGastrointestinal motility and disorders

Ca 2+ -induced contraction of cat esophageal circular smooth muscle cells

Cao, W., Chen, Q., Sohn, U. D., Kim, N., Kirber, M. T., Harnett, K. M., Behar, J., Biancani, P.·2001·American Journal of Physiology-Cell Physiology

DOI 10.1152/ajpcell.2001.280.4.c980

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Abstract

ACh-induced contraction of esophageal circular muscle (ESO) depends on Ca2+ influx and activation of protein kinase Cepsilon (PKCepsilon). PKCepsilon, however, is known to be Ca2+ independent. To determine where Ca2+ is needed in this PKCepsilon-mediated contractile pathway, we examined successive steps in Ca2+-induced contraction of ESO muscle cells permeabilized by saponin. Ca2+ (0.2-1.0 microM) produced a concentration-dependent contraction that was antagonized by antibodies against PKCepsilon (but not by PKCbetaII or PKCgamma antibodies), by a calmodulin inhibitor, by MLCK inhibitors, or by GDPbetas. Addition of 1 microM Ca2+ to permeable cells caused myosin light chain (MLC) phosphorylation, which was inhibited by the PKC inhibitor chelerythrine, by D609 [phosphatidylcholine-specific phospholipase C inhibitor], and by propranolol (phosphatidic acid phosphohydrolase inhibitor). Ca2+-induced contraction and diacylglycerol (DAG) production were reduced by D609 and by propranolol, alone or in combination. In addition, contraction was reduced by AACOCF(3) (cytosolic phospholipase A(2) inhibitor). These data suggest that Ca2+ may directly activate phospholipases, producing DAG and arachidonic acid (AA), and PKCepsilon, which may indirectly cause phosphorylation of MLC. In addition, direct G protein activation by GTPgammaS augmented Ca2+-induced contraction and caused dose-dependent production of DAG, which was antagonized by D609 and propranolol. We conclude that agonist (ACh)-induced contraction may be mediated by activation of phospholipase through two distinct mechanisms (increased intracellular Ca2+ and G protein activation), producing DAG and AA, and activating PKCepsilon-dependent mechanisms to cause contraction.

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Elevated intracellular Ca2+ levels activate PKC, resulting in smooth muscle contraction.
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Authors: Cao, W., Chen, Q., Sohn, U. D., Kim, N., Kirber, M. T., Harnett, K. M., Behar, J., & Biancani, P.
Affiliations: Brown University (US)
Chung-Ang University (KR)
Department of Internal Medicine, Kangnam General Hospital, Public Corporation, Seoul 135-090, Korea
ORCID: Cao, W.
Chen, Q.
Sohn, U. D.
Kirber, M. T.
Harnett, K. M.
Venue: American Journal of Physiology-Cell Physiology
Publisher: American Physiological Society
Published: 2001-04-01
Volume: 280
Issue: 4
Pages: C980-C992
ISSN: 0363-6143 (ISSN-L)
1522-1563
DOI: 10.1152/ajpcell.2001.280.4.c980
OpenAlex: W1863334369
Cited by: 28
References: 66
Citations by year: 2026: 1 · 2024: 2 · 2017: 1 · 2015: 1 · 2014: 2 · 2012: 1
FWCI: 1.16
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Cell Physiology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r29dk047223-05)
National Institute of Diabetes and Digestive and Kidney Diseases (DK47223, DK-26814)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: calcium-induced contraction, protein kinase C epsilon, acetylcholine, myosin light chain phosphorylation, diacylglycerol, arachidonic acid, phospholipase activation, G protein activation, saponin-permeabilized cells, chelerythrine, propranolol, D609, phosphatidylcholine-specific phospholipase C, phosphatidic acid phosphohydrolase
MeSH terms: Adrenergic beta-Antagonists, Alkaloids, Animals, Antibodies, Azepines, Bridged-Ring Compounds, Calcium, Cats, Dose-Response Relationship, Drug, Enzyme Inhibitors, Esophagus, Estrenes, Female, Isoenzymes, Male, Muscle Contraction, Muscle, Smooth, Naphthalenes, Norbornanes, Phenanthridines, Phosphodiesterase Inhibitors, Type C Phospholipases, Phospholipase D, Phosphorylation, Propranolol, Protein Kinase C, Pyrrolidinones, Quercetin, Thiocarbamates, Thiones, Second Messenger Systems, Guanosine 5'-O-(3-Thiotriphosphate), Myosin Light Chains, Calcium Signaling, Protein Kinase C-epsilon, Benzophenanthridines

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Ca 2+ -induced contraction of cat esophageal circular smooth muscle cells

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