BIOMAT Database Logo BIOMAT Database Logo

Modulation of Ca2+ sensitivity by cyclic nucleotides in smooth muscle from protein kinase G-deficient mice. 2004

Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
Department of Physiological Sciences, Martinsried, Munich 82152, Germany.

The cGMP-dependent protein kinase (PKG) is the main mediator of nitric oxide-induced relaxation of smooth muscle. Although this pathway is well established, the cellular action of PKG, nitric oxide, and cGMP is complex and not fully understood. A cross-talk between the cGMP-PKG and other pathways (e.g. cAMP-protein kinase A) seems to exist. We have explored cGMP- and cAMP-dependent relaxation of smooth muscle using PKG-deficient mice (cGKI-/-). In intact ileum strips of wild type mice (cGKI+/+), 8-Br-cGMP inhibited the sustained phase of carbachol contractions by approximately 80%. The initial peak was less inhibited (approximately 30%). This relaxation was associated with a reduction in intracellular [Ca2+] and decreased Ca2+ sensitivity. Contractions of cGKI-/- ileum were not influenced by 8-Br-cGMP. EC50 for 8-Br-cGMP for PKG was estimated to be 10 nm. PKG-independent relaxation by 8-Br-cGMP had an EC50 of 10 microm. Relaxation by cAMP (approximately 50% at 100 microm), Ca2+ sensitivity of force, and force potentiation by GTPgammaS were similar in cGKI+/+ and cGKI-/- tissues. The results show that PKG is the main target for cGMP-induced relaxation in intestinal smooth muscle. cGMP desensitize the contractile system to Ca2+ via PKG. PKG-independent pathways are activated at 1000-fold higher cGMP concentrations. Relaxation by cAMP can occur independently of PKG. Long term deficiency of PKG does not lead to an apparent up-regulation of the cAMP-dependent pathways or changes in Ca2+ sensitivity.

UI MeSH Term Description Entries
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D009711 Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed) Nucleotide
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006152 Cyclic GMP Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed) Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
Modulation of Ca2+ sensitivity by agonists in smooth muscle.
January 1991, Advances in experimental medicine and biology,
Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
Modulation of Ca2+ sensitivity in smooth muscle by genistein and protein tyrosine phosphorylation.
July 1995, Archives of biochemistry and biophysics,
Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
A multisubstrate Ca2+ and cyclic nucleotide independent kinase from vascular smooth muscle: modulation of activity by polycations.
April 1986, Biochemical and biophysical research communications,
Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
cGMP modulation of Ca2+ sensitivity in airway smooth muscle.
January 1999, The American journal of physiology,
Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
Cyclic nucleotides and smooth muscle.
January 1974, Advances in cyclic nucleotide research,
Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
Modulation of nucleocytosolic [Ca2+] gradient in smooth muscle by protein phosphorylation.
August 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
Protein kinase C modulation of cyclic GMP in rat neonatal pulmonary vascular smooth muscle.
January 2004, Lung,
Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
Regulation of the plasma membrane Ca2+ pump by cyclic nucleotides in cultured vascular smooth muscle cells.
June 1988, The Journal of biological chemistry,
Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
Influence of cyclic nucleotides on protein synthesis in vascular smooth muscle.
May 1976, Experientia,
Johan Bonnevier, and Reinhard Fässler, and Andrew P Somlyo, and Avril V Somlyo, and Anders Arner
Halothane reduces force and intracellular Ca2+ in airway smooth muscle independently of cyclic nucleotides.
February 1995, The American journal of physiology,
Copied contents to your clipboard!