title: Kinetics of relaxation by cGMP/cGKI signaling in fundus smooth muscle.
abstract: 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.
authors.affiliation: FOR923, Institut für Pharmakologie und Toxikologie, Technische Universität München, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ertl
authors.forename: Robert
authors.initials: R
authors.lastname: Lukowski
authors.forename: Katja
authors.initials: K
authors.lastname: Sigl
authors.forename: Jens
authors.initials: J
authors.lastname: Schlossmann
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.forename: Jörg W
authors.initials: JW
authors.lastname: Wegener
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005748:Gastric Fundus; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; C015482:protein kinase modulator; C016276:8-bromocyclic GMP; D006152:Cyclic GMP