Expression of natriuretic peptides, nitric oxide synthase, and guanylate cyclase activity in frog mesonephros during the annual cycle

Cyclic GMP has been shown in recent years to directly activate ion channels in bipolar and ganglion cells, and to indirectly regulate coupling between horizontal cells, and between bipolar and amacrine cells. In all of these cases, the effects of cyclic GMP are mimicked by nitric oxide. An increase in calcium concentration stimulates the production of nitric oxide by neuronal and endothelial forms of nitric oxide synthase, which in turn activates soluble guanylate cyclases, enhancing the synthesis of cyclic GMP. Though some effects of nitric oxide do not involve cyclic GMP, the nitric oxide-cyclic GMP cascade is well recognized as a signaling mechanism in brain and other tissues. The widespread occurrence of nitric oxide/cyclic GMP-regulated ion channel activity in retinal neurons raises the possibility that nitric-oxide-sensitive soluble guanylate cyclases play an important role in cell–cell communication, and possibly, synaptic transmission. Immunohistochemical studies have indicated the presence of soluble guanylate cyclase in retinal synaptic layers, but such studies are not suitable for determination of the density or quantitative subcellular distribution of the enzyme. Microanalytical methods involving microdissection of frozen retina also showed the presence of cyclase activity in retinal plexiform layers but these methods did not permit distinction between nitric oxide-sensitive and insensitive cyclases. In this study, we fractionated retinal homogenate into the cytosolic and synaptosomal fractions and investigated the specific activity and distribution of soluble guanylate cyclase and nitric oxide synthase. The results show that both enzymes are present in the synaptosomal fractions derived from inner and outer plexiform layers. The synaptosomal fraction derived from inner retina was highly enriched in cyclase activity. Nitric oxide synthase activity was also higher in the inner than outer retinal synaptosomal fraction. The results suggest that the nitric oxide-cyclic GMP system is operational in both synaptic layers of retina and that it may play a more significant role in the inner retina.

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Localization of natriuretic peptides and their activation of particulate guanylate cyclase and nitric oxide synthase in the retina

The Journal of Comparative Neurology ◽

10.1002/1096-9861(20000904)424:4<689::aid-cne10>3.0.co;2-k ◽

2000 ◽

Vol 424 (4) ◽

pp. 689-700 ◽

Cited By ~ 18

Author(s):

Todd A. Blute ◽

Hoi Ko Lee ◽

Trevor Huffmaster ◽

Silke Haverkamp ◽

William D. Eldred

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Guanylate Cyclase ◽

Natriuretic Peptides ◽

Oxide Synthase

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Measurement of nitric oxide synthase activity in sections of rat liver.

Journal of Histochemistry & Cytochemistry ◽

10.1177/43.12.8537639 ◽

1995 ◽

Vol 43 (12) ◽

pp. 1229-1233 ◽

Cited By ~ 4

Author(s):

S Mehdizadeh ◽

A O'Farrell ◽

L Bitensky ◽

J Weisz ◽

J Alaghband-Zadeh ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Rat Liver ◽

Guanylate Cyclase ◽

Kupffer Cells ◽

Soluble Guanylate Cyclase ◽

Reaction Medium ◽

Guanylate Cyclase Activity ◽

Oxide Synthase ◽

Nitric Oxide Synthase Activity

In the previous communication we described a histochemical method for measuring soluble guanylate cyclase (sGC) activity in sections of rat liver. In theory, this method could be used to assess nitric oxide synthase (NOS) activity by the increased sGC activity induced by the additional presence of the substrates for NOS activity. We found that this was correct provided that the concentration of the colloid stabilizer in the reaction medium was decreased to just below the concentration required to fully stabilize the guanylate cyclase activity in the sections. This was related to the fact that the site of NOS activity was different from that of the sGC activity in the hepatocytes, so that the NO generated had to diffuse from the Kupffer cells to the hepatocytes as could occur only in partially unstabilized sections. Optimal concentrations of arginine and of NADPH have been determined for demonstrating NOS activity; the increased reaction was shown to be largely inhibited by methyl-arginine.

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Nitric oxide synthase and soluble guanylate cyclase are involved in spinal cord wind-up activity of monoarthritic, but not of normal rats

Neuroscience Letters ◽

10.1016/s0304-3940(03)01000-0 ◽

2003 ◽

Author(s):

C Laurido

Keyword(s):

Nitric Oxide ◽

Spinal Cord ◽

Nitric Oxide Synthase ◽

Guanylate Cyclase ◽

Soluble Guanylate Cyclase ◽

Oxide Synthase

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Inhibition of nitric oxide synthase and soluble guanylate cyclase induces cardiodepressive effects in normal rat hearts

European Journal of Pharmacology ◽

10.1016/s0014-2999(97)01168-0 ◽

1997 ◽

Vol 334 (2-3) ◽

pp. 181-190 ◽

Cited By ~ 39

Author(s):

Georg Kojda ◽

Karin Kottenberg ◽

Eike Noack

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Guanylate Cyclase ◽

Soluble Guanylate Cyclase ◽

Rat Hearts ◽

Normal Rat ◽

Oxide Synthase

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Abstract 1415: Activation of Soluble Guanylate Cyclase Regulates Phosphodiesterase 5A Localization and Restores Anti-adrenergic Action of Sildenafil despite Nitric Oxide Synthase Inhibition

Circulation ◽

10.1161/circ.116.suppl_16.ii_291 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Takahiro Nagayama ◽

Manling Zhang ◽

Eiki Takimoto ◽

David A Kass

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Guanylate Cyclase ◽

Cyclic Gmp ◽

Soluble Guanylate Cyclase ◽

Synergistic Effects ◽

Adrenergic Stimulation ◽

Adrenergic Activity ◽

Oxide Synthase

Background: We have shown that inhibition of cyclic GMP-phosphodiesterase 5A (PDE5A) by sildenafil (SIL) blunts cardiomyocyte β-adrenergic stimulation, but this effect depends on the activity of endothelial nitric oxide synthase (eNOS) to generate a specific pool of cyclic GMP. PDE5A normally localizes at Z-bands in myocytes, but localization is more diffuse in cells with eNOS chronically inhibited. Here, we tested whether the influence of eNOS on PDE5A localization and anti-adrenergic action depends upon cyclic GMP. Methods and Results: Mouse in vivo hemodynamics were assessed by pressure-volume analysis. Isoproterenol (ISO: 20 ng/kg/min, iv ) stimulated contractility was inhibited by SIL (100 μg/kg/min, iv ), however this did not occur in mice given N w -nitro-L-arginine methyl ester (L-NAME: 1 mg/mL in drinking water for 1 week) to inhibit NOS. Myocytes transfected with an adenoviral vector encoding a fusion protein (PDE5A-DSred) in vivo were subsequently isolated and examined for PDE5A/α-actinin localization. Normal cells showed strong co-localization, whereas L-NAME-treated cells had diffuse PDE5A distribution. If L-NAME was stopped for 1-wk washout, SIL regained anti-adrenergic activity, and PDE5A z-band localization was restored. If L-NAME was continued but combined with Bay 41– 8543 (BAY: 30 mg/kg/day, po ), a soluble guanylate cyclase (sGC) activator, both PDE5A localization and SIL anti-adrenergic action were also restored. Chronic L-NAME suppressed phosphorylation of vasodilator-stimulated protein (VASP), a marker of protein kinase G (PKG) activity, in hearts acutely exposed to ISO+SIL. After L-NAME washout or L-NAME+BAY, VASP phosphorylation with ISO+SIL was restored. Conclusion: NOS-dependent modulation of both PDE5A sarcomere localization and anti-adrenergic activity depends upon sGC-derived cyclic GMP, and is linked to PKG activation. This suggests sGC activators may have synergistic effects with PDE5A inhibitors.

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