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Kinetics of relaxation by cGMP/cGKI signaling in fundus smooth muscle

cGMP-dependent kinase I (cGKI) is a major mediator of smooth muscle relaxation and exists in two isoforms, α and β. Both isoforms are supposed to mediate their effects via different intracellular signaling pathways. To verify this concept, the kinetics of relaxation mediated by either isoform was an...

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Published in:European journal of pharmacology 2011-11, Vol.670 (1), p.266-271
Main Authors: Ertl, Claudia, Lukowski, Robert, Sigl, Katja, Schlossmann, Jens, Hofmann, Franz, Wegener, Jörg W.
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container_title European journal of pharmacology
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creator Ertl, Claudia
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description cGMP-dependent kinase I (cGKI) is a major mediator of smooth muscle relaxation and exists in two isoforms, α and β. Both isoforms are supposed to mediate their effects via different intracellular signaling pathways. To verify this concept, the kinetics of relaxation mediated by either isoform was analyzed in gastric fundus smooth muscle from mice. Muscles from mice that express selectively the Iα or Iβ isoform of cGKI in smooth muscle (sm-cGKIα or sm-cGKIβ mice) were compared to muscles from conventional cGKI−/− mice. Fundus muscles were contracted by carbachol and then relaxed by 8-Br-cGMP or by electrical field stimulation (EFS). The time course of relaxation by 8-Br-cGMP was not different between muscles from sm-cGKIα and sm-cGKIβ mice. EFS induced a fast transient relaxation in muscles from sm-cGKIα and sm-cGKIβ mice that was blocked by the NO synthase inhibitor L-NAME. Recovery from this relaxation was about 4-times slower in muscles from sm-cGKIα mice than in muscles from sm-cGKIβ mice. The different kinetic of recovery from relaxation after EFS in sm-cGKIα and sm-cGKIβ mice suggests that different signaling pathways exist for each cGKI isoform in vivo in fundus muscles.
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subjects Animals
Biological and medical sciences
cGMP
Cyclic GMP - analogs & derivatives
Cyclic GMP - metabolism
Cyclic GMP - pharmacology
Electric Stimulation
Female
Fundus
Gastric Fundus
Gene Expression Regulation - drug effects
In Vitro Techniques
Intracellular Signaling Peptides and Proteins - metabolism
Kinetics
Male
Medical sciences
Mice
Muscle Relaxation - drug effects
Muscle, Smooth - cytology
Muscle, Smooth - drug effects
Muscle, Smooth - metabolism
Muscle, Smooth - physiology
NANC
Neurons - drug effects
Neurons - metabolism
Nitric oxide
Pharmacology. Drug treatments
Protein Isoforms - metabolism
Relaxation
Signal Transduction - drug effects
title Kinetics of relaxation by cGMP/cGKI signaling in fundus smooth muscle
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