CaM kinase II activation and phospholamban phosphorylation by SNP in murine gastric antrum smooth muscles.
Elevations in the intracellular Ca(2+) concentration activate the serine/threonine protein kinase Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II). We tested the hypothesis that increased sarco(endo)plasmic reticulum Ca(2+)-ATPase activity by phospholamban (PLB) phosphorylation contributes to smooth muscle relaxation by elevating the sarcoplasmic reticulum (SR) Ca(2+) load and increasing the frequency of Ca(2+) release events from the SR. We have previously shown that caffeine or sodium nitroprusside (SNP) relaxes murine gastric fundus smooth muscles and increases PLB phosphorylation by CaM kinase II. These findings suggest that an increased SR Ca(2+) load increases the frequency of Ca(2+) transients from the SR and results in PLB phosphorylation by CaM kinase II, contributing to caffeine- or SNP-induced relaxation. The aim of the present study was to investigate the effects of SNP on CaM kinase II and PLB phosphorylation in gastric antrum smooth muscles. SNP or 8-bromo-cGMP decreased the basal tone and amplitudes of spontaneous phasic contractions and activated CaM kinase II. SNP-induced relaxation and CaM kinase II activation were blocked by [1,2,4]oxadizolo-[4,3alpha]quinoxaline-1-one (ODQ) and inhibited by cyclopiazonic acid (CPA) or KN-93. SNP also increased PLBSer(16) and PLBThr(17) phosphorylation. Both PLBSer(16) and Thr(17) phosphorylation were ODQ sensitive. However, only PLBThr(17) phosphorylation was inhibited by CPA or KN-93. These results suggest that CaM kinase II activation and PLB phosphorylation participate in the relaxant effect of SNP on murine gastric antrum smooth muscles through a nitric oxide/guanylyl cyclase/cGMP pathway.
Kim
Minkyung
M
Department of Physiology and Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Anderson Bldg., MS352, Reno, NV 89557, USA.
Perrino
Brian A
BA
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D013449:Sulfonamides / Q000494:pharmacology; D000099211:Phospholamban; D000096926:Benzenesulfonamides
D001596:Benzylamines; D002135:Calcium-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D006152:Cyclic GMP; D017869:Cyclic GMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D006162:Guanylate Cyclase; D007211:Indoles; D009569:Nitric Oxide; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D018160:Receptors, Cytoplasmic and Nuclear; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000071756:Soluble Guanylyl Cyclase; D013449:Sulfonamides; D000099211:Phospholamban; C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C072105:KN 93; D000096926:Benzenesulfonamides; C016276:8-bromocyclic GMP; C000543:cyclopiazonic acid