Pulmonary soluble guanylate cyclase, a nitric oxide receptor, is increased during the perinatal period

1997 ◽  
Vol 272 (3) ◽  
pp. L400-L406 ◽  
Author(s):  
K. D. Bloch ◽  
G. Filippov ◽  
L. S. Sanchez ◽  
M. Nakane ◽  
S. M. de la Monte
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Muscle Cells ◽  
Perinatal Period ◽  
Mrna Levels ◽  
Old Rats ◽  
Beta1 Subunit

Nitric oxide (NO) has an important role in the pulmonary vasodilatation associated with the transition from fetal to neonatal life. NO activates pulmonary soluble guanylate cyclase (sGC), an obligate heterodimer composed of alpha1- and beta1-subunits, increasing synthesis of guanosine 3',5'-cyclic monophosphate (cGMP) and leading to vasodilation. In this study, regulation of sGC subunit expression during pulmonary development was examined. RNA blot hybridization revealed abundant alpha1- and beta1-subunit mRNA in lungs of late-gestation fetal and neonatal Sprague-Dawley rats, with markedly reduced levels detected in adult lungs. Pulmonary sGC enzyme activity in the presence of 1 mM sodium nitroprusside, a NO-donor compound, was approximately sevenfold greater in 1- and 8-day-old rats than in adult rats (P < 0.03). With the use of immunoblot techniques, pulmonary alpha1-subunit concentrations closely correlated with mRNA levels. With in situ hybridization, alpha1- and beta1-subunit mRNAs were readily detected in pulmonary vascular and bronchial smooth muscle cells as well as alveolar and serosal epithelial cells in lungs of 1-day-old rats. In adult lungs, sGC subunit mRNAs were present at low levels and were found nearly exclusively in bronchial and vascular smooth muscle cells. These results demonstrate that abundant pulmonary sGC is available to respond to the increased NO produced during the perinatal period. High-level expression of sGC subunit genes outside the vasculature of lungs of 1-day-old rats suggests an important role for NO-cGMP signal transduction in the perinatal regulation of pulmonary epithelial function and bronchial tone.

Nitric oxide induces phosphodiesterase 4B expression in rat pulmonary artery smooth muscle cells

2006 ◽  
Vol 290 (4) ◽  
pp. L747-L753 ◽  
Author(s):  
Cornelius J. Busch ◽  
Heling Liu ◽  
Amanda R. Graveline ◽  
Kenneth D. Bloch
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Dominant Negative ◽  
Mrna Levels ◽  
Dependent Manner ◽  
The Impact

Phosphodiesterases (PDE) metabolize cyclic nucleotides limiting the effects of vasodilators such as prostacyclin and nitric oxide (NO). In this study, DNA microarray techniques were used to assess the impact of NO on expression of PDE genes in rat pulmonary arterial smooth muscle cells (rPASMC). Incubation of rPASMC with S-nitroso-l-glutathione (GSNO) increased expression of a PDE isoform that specifically metabolizes cAMP (PDE4B) in a dose- and time-dependent manner. GSNO increased PDE4B protein levels, and rolipram-inhibitable PDE activity was 2.3 ± 1.0-fold greater in GSNO-treated rPASMC than in untreated cells. The soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one, and the cAMP-dependent protein kinase inhibitor, H89, prevented induction of PDE4B gene expression by GSNO, but the protein kinase G (PKG) inhibitors, Rp-8-pCPT-cGMPs and KT-5823, did not. Incubation of rPASMC with IL-1β and tumor necrosis factor-α induced PDE4B gene expression, an effect that was inhibited by l- N6-(1-iminoethyl)lysine, an antagonist of NO synthase 2 (NOS2). The GSNO-induced increase in PDE4B mRNA levels was blocked by actinomycin D but augmented by cycloheximide. Infection of rPASMC with an adenovirus specifying a dominant negative cAMP response element binding protein (CREB) mutant inhibited the GSNO-induced increase of PDE4B gene expression. These results suggest that exposure of rPASMC to NO induces expression of PDE4B via a mechanism that requires cGMP synthesis by sGC but not PKG. The GSNO-induced increase of PDE4B gene expression is CREB dependent. These findings demonstrate that NO increases expression of a cAMP-specific PDE and provide evidence for a novel “cross talk” mechanism between cGMP and cAMP signaling pathways.

Hypoxia Decreases Expression of Soluble Guanylate Cyclase in Cultured Rat Pulmonary Artery Smooth Muscle Cells

2004 ◽  
Vol 30 (6) ◽  
pp. 908-913 ◽  
Author(s):  
Paul M. Hassoun ◽  
Galina Filippov ◽  
Michael Fogel ◽  
Cameron Donaldson ◽  
Usamah S. Kayyali ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Muscle Cells ◽  
Pulmonary Artery Smooth Muscle

scholarly journals THE ROLE OF CARBON MONOXIDE IN THE REGULATION OF ELECTRICAL AND CONTRACTILE PROPERTIES OF SMOOTH MUSCLE CELLS OF THE GUINEA PIG URETER

2014 ◽  
Vol 13 (1) ◽  
pp. 39-46
Author(s):  
I. V. Kovalyov ◽  
M. B. Baskakov ◽  
S. V. Gusakova ◽  
T. A. Idamzhapova ◽  
Yu. G. Birulina ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Smooth Muscle ◽  
Guinea Pig ◽  
Smooth Muscle Cells ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Smooth Muscles ◽  
Muscle Cells ◽  
Contractile Properties ◽  
Biologically Active

Carbon monoxide CO, as well as nitric oxide and hydrogen sulfide, make up the family of labile biological mediators termed gasotransmitters. We hypothesized that CO may be involved in the mechanisms of regulation electrical and contractile properties of smooth muscles.The effects of carbon monoxide donor CORM II (tricarbonyldichlororuthenium(II)-dimer) on the electrical and contractile activities of smooth muscles of the guinea pig ureter were studied by the method of the double sucrose bridge. This method allows to register simultaneously the parameters of the action potential (AP) and the contraction of smooth muscle cells (SMCs), caused by an electrical stimulus.CORM II in a concentration of 10 mmol has reduced the amplitude of contractions SMCs to (86.5 ± 9.7)% (n = 6, p < 0.05), the amplitude of the AP to (88.9 ± 4.2)% (n = 6, p < 0.05) and the duration of the plateau of the AP to (91.7 ± 6.0)% (n = 6, p < 0.05). On the background of the action of biologically active substances (phenylephrine, 10 µmol or histamine, 10 µmol), these effects of CORM II amplified. The inhibitory action of СORM II on the parameters of the contractile and electrical activities of the smooth muscles of guinea pig ureter has been decreased by blocking potassium channels in membrane of SMCs by tetraethylammonium chloride (TEA) оr inhibition of soluble guanylate cyclase (ODQ [1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-l-one]). On the background of TEA (5 mmol), a donor of CO (10 mmol) caused a reduction the amplitude of contraction SMCs to (87.0 ± 10.8)% (n = 6, p < 0.05), the amplitude of the AP to (91.7 ± 6.4)% (n = 6, p < 0.05) and the duration of the plateau of the AP to (93.4 ± 7.5)% (n = 6, p < 0.05). After the pretreatment of ODQ (1 µmol) adding CORM II (10 mmol) in solution has resulted to augment of the amplitude of contraction ureteral smooth muscle strips to (90.9 ± 4.2)% (n = 6, p < 0.05), the amplitude of the AP to (97.2 ± 10.3)% (n = 6, p < 0.05) and the duration of the plateau of the AP to and (99.7 ± 10.0)% (n = 6, p < 0.05).Thus, can be argued the inhibitory effect of carbon monoxide on the electrical and contractile activities of the guinea pig ureter SMCs is due to changes in the ionic conductivity of the membranes, above all with increasing the potassium conductance or activation of soluble guanylate cyclase.

Sign in / Sign up

Export Citation Format

Share Document