In Vitro Activation of Soluble Guanylyl Cyclase and Nitric Oxide Release:  A Comparison of NO Donors and NO Mimetics†

Biochemistry ◽  
2001 ◽  
Vol 40 (31) ◽  
pp. 9256-9264 ◽  
Author(s):  
Jennifer D. Artz ◽  
Violeta Toader ◽  
Sergei I. Zavorin ◽  
Brian M. Bennett ◽  
Gregory R. J. Thatcher
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
No Donors ◽  
Nitric Oxide Release ◽  
In Vitro Activation

Modulation of Neuronal Nitric Oxide Release by Soluble Guanylyl Cyclase in Guinea Pig Colon

2001 ◽  
Vol 280 (4) ◽  
pp. 1130-1134 ◽  
Author(s):  
K. Hallén ◽  
C. Olgart ◽  
L.E. Gustafsson ◽  
N.P. Wiklund
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Nitric Oxide Release

scholarly journals Biphasic roles for soluble guanylyl cyclase (sGC) in platelet activation

Blood ◽  
2011 ◽  
Vol 118 (13) ◽  
pp. 3670-3679 ◽  
Author(s):  
Guoying Zhang ◽  
Binggang Xiang ◽  
Anping Dong ◽  
Radek C. Skoda ◽  
Alan Daugherty ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Whole Body ◽  
No Donor ◽  
No Donors ◽  
Deficient Mice

AbstractNitric oxide (NO) stimulates cGMP synthesis by activating its intracellular receptor, soluble guanylyl cyclase (sGC). It is a currently prevailing concept that No and cGMP inhibits platelet function. However, the data supporting the inhibitory role of NO/sGC/cGMP in platelets have been obtained either in vitro or using whole body gene deletion that affects vessel wall function. Here we have generated mice with sGC gene deleted only in megakaryocytes and platelets. Using the megakaryocyte- and platelet-specific sGC-deficient mice, we identify a stimulatory role of sGC in platelet activation and in thrombosis in vivo. Deletion of sGC in platelets abolished cGMP production induced by either NO donors or platelet agonists, caused a marked defect in aggregation and attenuated secretion in response to low doses of collagen or thrombin. Importantly, megakaryocyte- and platelet-specific sGC deficient mice showed prolonged tail-bleeding times and impaired FeCl3-induced carotid artery thrombosis in vivo. Interestingly, the inhibitory effect of the NO donor SNP on platelet activation was sGC-dependent only at micromolar concentrations, but sGC-independent at millimolar concentrations. Together, our data demonstrate important roles of sGC in stimulating platelet activation and in vivo thrombosis and hemostasis, and sGC-dependent and -independent inhibition of platelets by NO donors.

Nitric oxide dilates rat retinal blood vessels by cyclooxygenase-dependent mechanisms

2009 ◽  
Vol 297 (4) ◽  
pp. R968-R977 ◽  
Author(s):  
Naoto Ogawa ◽  
Asami Mori ◽  
Masami Hasebe ◽  
Maya Hoshino ◽  
Maki Saito ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Vessel ◽  
Blood Vessels ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Retinal Blood Vessel ◽  
No Donors ◽  
Retinal Blood Vessels ◽  
Retinal Arterioles ◽  
Cox 1

It has been suggested that nitric oxide (NO) stimulates the cyclooxygenase (COX)-dependent mechanisms in the ocular vasculature; however, the importance of the pathway in regulating retinal circulation in vivo remains to be elucidated. Therefore, we investigated the role of COX-dependent mechanisms in NO-induced vasodilation of retinal blood vessels in thiobutabarbital-anesthetized rats with and without neuronal blockade (tetrodotoxin treatment). Fundus images were captured with a digital camera that was equipped with a special objective lens. The retinal vascular response was assessed by measuring changes in diameter of the retinal blood vessel. The localization of COX and soluble guanylyl cyclase in rat retina was examined using immunohistochemistry. The NO donors (sodium nitroprusside and NOR3) increased the diameter of the retinal blood vessels but decreased systemic blood pressure in a dose-dependent manner. Treatment of rats with indomethacin, a nonselective COX inhibitor, or SC-560, a selective COX-1 inhibitor, markedly attenuated the vasodilation of retinal arterioles, but not the depressor response, to the NO donors. However, both the vascular responses to NO donors were unaffected by the selective COX-2 inhibitors NS-398 and nimesulide. Indomethacin did not change the retinal vascular and depressor responses to hydralazine, 8-(4-chlorophenylthio)-guanosine-3′, 5′-cyclic monophosphate (a membrane-permeable cGMP analog) and 8-(4-chlorophenylthio)-adenosine-3′, 5′-cyclic monophosphate (a membrane-permeable cAMP analog). Treatment with SQ 22536, an adenylyl cyclase inhibitor, but not ODQ, a soluble guanylyl cyclase inhibitor, significantly attenuated the NOR3-induced vasodilation of retinal arterioles. The COX-1 immunoreactivity was found in retinal blood vessels. The retinal blood vessel was faintly stained for soluble guanylyl cyclase, although the apparent immunoreactivities on mesenteric and choroidal blood vessels were observed. These results suggest that NO exerts a substantial part of its dilatory effect via a mechanism that involves COX-1-dependent pathway in rat retinal vasculature.

Chaperone-dependent E3 ligase CHIP ubiquitinates and mediates proteasomal degradation of soluble guanylyl cyclase

2007 ◽  
Vol 293 (5) ◽  
pp. H3080-H3087 ◽  
Author(s):  
Tian Xia ◽  
Christiana Dimitropoulou ◽  
Jingmin Zeng ◽  
Galina N. Antonova ◽  
Connie Snead ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Guanylyl Cyclase ◽  
Vascular Function ◽  
E3 Ligase ◽  
Soluble Guanylyl Cyclase ◽  
Proteasomal Degradation ◽  
Nitric Oxide Donor

The nitric oxide receptor soluble guanylyl cyclase (sGC) exists in multimeric protein complexes, including heat shock protein (HSP) 90 and endothelial nitric oxide synthase. Inhibition of HSP90 by geldanamycin causes proteasomal degradation of sGC protein. In this study, we have investigated whether COOH terminus of heat shock protein 70-interacting protein (CHIP), a co-chaperone molecule that is involved in protein folding but is also a chaperone-dependent ubiquitin E3 ligase, could play a role in the process of degradation of sGC. Transient overexpression of CHIP in COS-7 cells degraded heterologous sGC in a concentration-related manner; this downregulation of sGC was abrogated by the proteasome inhibitor MG-132. Transfection of tetratricopeptide repeats and U-box domain CHIP mutants attenuated sGC degradation, suggesting that both domains are indispensable for CHIP function. Results from immunoprecipitation and indirect immunofluorescent microscopy experiments demonstrated that CHIP is associated with sGC, HSP90, and HSP70 in COS-7 cells. Furthermore, CHIP increased the association of HSP70 with sGC. In in vitro ubiquitination assays using purified proteins and ubiquitin enzymes, E3 ligase CHIP directly ubiquitinated sGC; this ubiquitination was potentiated by geldanamycin in COS-7 cells, followed by proteasomal degradation. In rat aortic smooth muscle cells, endogenous sGC was also degraded by adenovirus-infected wild-type CHIP but not by the chaperone interaction-deficient K30A CHIP, whereas CHIP, but not K30A, attenuated sGC expression in, and nitric oxide donor-induced relaxation of, rat aortic rings, suggesting that CHIP plays a regulatory role under physiological conditions. This study reveals a new mechanism for the regulation of sGC, an important mediator of cellular and vascular function.

2055 MECHANISMS OF RELAXANT ACTIVITY OF THE NITRIC OXIDE-INDEPENDENT SOLUBLE GUANYLYL CYCLASE STIMULATOR BAY 41-2272 IN ISOLATED HUMAN URETER: AN IN VITRO STUDY

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
Ricardo Miyaoka ◽  
Fabiola Monica ◽  
Gilberto de Nucci ◽  
Carlos D'Ancona ◽  
Edson Antunes
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
In Vitro Study ◽  
Vitro Study ◽  
Human Ureter

scholarly journals Cyclic Guanosine Monophosphate Modulates Locomotor Acceleration Induced by Nitric Oxide but not Serotonin in Clione limacina Central Pattern Generator Swim Interneurons

2020 ◽  
Author(s):  
Thomas J Pirtle ◽  
Richard A Satterlie
Keyword(s):  
Nitric Oxide ◽  
Central Pattern Generator ◽  
Guanylyl Cyclase ◽  
Signal Transduction Pathway ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Pattern Generator ◽  
Guanosine Monophosphate ◽  
Cellular Changes ◽  
Clione Limacina

Abstract Typically, the marine mollusk, Clione limacina, exhibits a slow, hovering locomotor gait to maintain its position in the water column. However, the animal exhibits behaviorally relevant locomotor swim acceleration during escape response and feeding behavior. Both nitric oxide and serotonin mediate this behavioral swim acceleration. In this study, we examine the role that the second messenger, cGMP, plays in mediating nitric oxide and serotonin-induced swim acceleration. We observed that the application of an analog of cGMP or an activator of soluble guanylyl cyclase increased fictive locomotor speed recorded from Pd-7 interneurons of the animal’s locomotor central pattern generator. Moreover, inhibition of soluble guanylyl cyclase decreased fictive locomotor speed. These results suggest that basal levels of cGMP are important for slow swimming and that increased production of cGMP mediates swim acceleration in Clione. Because nitric oxide has its effect through cGMP signaling and because we show herein that cGMP produces cellular changes in Clione swim interneurons that are consistent with cellular changes produced by serotonin application, we hypothesize that both nitric oxide and serotonin function via a common signal transduction pathway that involves cGMP. Our results show that cGMP mediates nitric oxide-induced but not serotonin-induced swim acceleration in Clione.

scholarly journals Nitric Oxide Activates the β2Subunit of Soluble Guanylyl Cyclase in the Absence of a Second Subunit

2001 ◽  
Vol 276 (33) ◽  
pp. 30737-30743 ◽  
Author(s):  
Markus Koglin ◽  
Kai Vehse ◽  
Lars Budaeus ◽  
Hasso Scholz ◽  
Sönke Behrends
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase
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