A Short History of cGMP, Guanylyl Cyclases, and cGMP-Dependent Protein Kinases

Kots, Alexander Y.; Martin, Emil; Sharina, Iraida; Murad, Ferid

doi:10.1007/978-3-540-68964-5_1

Cited by 80 publications

(53 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Soluble guanyl cyclase, which generates cGMP, was the first identified target for NO (37,52). NO binding to the heme group of soluble guanyl cyclase leads to increased conversion of GTP to cGMP, which in turn activates protein kinase G (PKG) to result ultimately in a reduction of cardiac contractility (47).…”

Section: Cgmp Regulates the Cardiac Effects Of Cstmentioning

confidence: 99%

Phosphodiesterase type-2 and NO-dependentS-nitrosylation mediate the cardioinhibition of the antihypertensive catestatin

Angelone¹,

Quintieri

Pasqua³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

The chromogranin A (CHGA)-derived peptide catestatin (CST: hCHGA(352-372)) is a noncompetitive catecholamine-release inhibitor that exerts vasodilator, antihypertensive, and cardiosuppressive actions. We have shown that CST directly influences the basal performance of the vertebrate heart where CST dose dependently induced a nitric oxide-cGMP-dependent cardiosuppression and counteracted the effects of adrenergic stimulation through a noncompetitive antagonism. Here, we sought to determine the specific intracardiac signaling activated by CST in the rat heart. Physiological analyses performed on isolated, Langendorff-perfused cardiac preparations revealed that CST-induced negative inotropism and lusitropism involve β(2)/β(3)-adrenergic receptors (β(2)/β(3)-AR), showing a higher affinity for β(2)-AR. Interaction with β(2)-AR activated phosphatidylinositol 3-kinase/endothelial nitric oxide synthase (eNOS), increased cGMP levels, and induced activation of phosphodiesterases type 2 (PDE2), which was found to be involved in the antiadrenergic action of CST as evidenced by the decreased cAMP levels. CST-dependent negative cardiomodulation was abolished by functional denudation of the endothelium with Triton. CST also increased the eNOS expression in cardiac tissue and human umbilical vein endothelial cells. cells, confirming the involvement of the vascular endothelium. In ventricular extracts, CST increased S-nitrosylation of both phospholamban and β-arrestin, suggesting an additional mechanism for intracellular calcium modulation and β-adrenergic responsiveness. We conclude that PDE2 and S-nitrosylation play crucial roles in the CST regulation of cardiac function. Our results are of importance in relation to the putative application of CST as a cardioprotective agent against stress, including excessive sympathochromaffin overactivation.

show abstract

Section: Cgmp Regulates the Cardiac Effects Of Cstmentioning

confidence: 99%

Phosphodiesterase type-2 and NO-dependentS-nitrosylation mediate the cardioinhibition of the antihypertensive catestatin

Angelone¹,

Quintieri

Pasqua³

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…The present results indicate that decreases in pulmonary and systemic arterial pressures in response to ACh are not mediated by the activation of sGC or TRPV4 channels and that ODQ can be used to study the role of the activation of sGC in mediating vasodilator responses in the rat. pulmonary vascular bed; transient receptor vanilloid type; vasodilation CYCLIC GUANOSINE MONOPHOSPHATE (cGMP) has an important role in the regulation of vascular smooth muscle tone and is synthesized from guanosine triphosphate (GTP) by soluble guanylate cyclase (sGC), the receptor for nitric oxide (NO) (2,29,32,41). sGC is a heterodimeric enzyme, and binding of NO to the heme-containing subunit activates sGC (2).…”

mentioning

confidence: 99%

Vasodilator responses to acetylcholine are not mediated by the activation of soluble guanylate cyclase or TRPV4 channels in the rat

Pankey

Kassan

Choi

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

The effects of 1H-[1,2,4]-oxadizaolo [4,3-]quinoxaline-1-one (ODQ), an inhibitor of the activation of soluble guanylate cyclase (sGC) on responses to NO donors acetylcholine (ACh) and bradykinin (BK) were investigated in the pulmonary and systemic vascular beds of the rat. In these studies the administration of ODQ in a dose of 5 mg/kg iv attenuated vasodilator responses to five different NO donors without inhibiting responses to ACh and BK in the systemic and pulmonary vascular beds of the rat. Vasodilator responses to ACh were not inhibited by L-NAME or the transient receptor vanilloid type 4 (TRPV4) antagonist GSK-2193874, which attenuated vasodilator responses to the TRPV4 agonist GSK-1016790A. ODQ did not inhibit vasodilator responses to agents reported to act in an NO-independent manner or to vasoconstrictor agents, and ODQ did not increase blood methemoglobin levels, suggesting that off target effects were minimal. These results show that ODQ in a dose that inhibited NO donor-mediated responses did not alter vasodilator responses to ACh in the pulmonary and systemic vascular beds and did not alter systemic vasodilator responses to BK. The present results indicate that decreases in pulmonary and systemic arterial pressures in response to ACh are not mediated by the activation of sGC or TRPV4 channels and that ODQ can be used to study the role of the activation of sGC in mediating vasodilator responses in the rat. pulmonary vascular bed; transient receptor vanilloid type; vasodilation CYCLIC GUANOSINE MONOPHOSPHATE (cGMP) has an important role in the regulation of vascular smooth muscle tone and is synthesized from guanosine triphosphate (GTP) by soluble guanylate cyclase (sGC), the receptor for nitric oxide (NO) (2,29,32,41). sGC is a heterodimeric enzyme, and binding of NO to the heme-containing subunit activates sGC (2). In contrast, oxidation of the heme-containing subunit reduces the sensitivity of the enzyme to NO (7,25,45,48,49). Pharmacological agents and genetic alterations that selectively modulate sGC activity are useful in the study of the physiological function of the enzyme in regulating vascular tone and mediating vasodilator responses (19,35,43).Although the role of NO in the regulation of baseline tone is well established, the role of NO in mediating vasodilator responses to acetylcholine (ACh) and bradykinin (BK) is controversial (4,12,34). A large number of studies show that vasorelaxant responses to ACh are mediated by the NO-cGMP pathway; however, other studies indicate that NO is not involved (13,18,20). It has been hypothesized that vessel size, vascular segment studied, method used, and species may account for differences in the role of NO in mediating responses to ACh and BK reported in the literature (17, 34). Studies in isolated first-order gracilis muscle arterioles from endothelial NOS (eNOS) knockout mice show that responses to ACh were only slightly attenuated, and studies in eNOS and cGMPdependent protein kinase type-1 (cGKI) knockout mice show that vasodepressor responses to...

show abstract

“…Sgc, a heterodimer consisting of α and β subunits, which is activated by the direct interaction of NO with the heme of the β subunit [13]. There is conclusive evidence that effect of low concentrations of NO is cgmp dependent [18,19].…”

Section: Discussionmentioning

confidence: 99%

Interaction of Cholera Toxin B Subunit with Intestinal Epithelial Cells

Navolotskaya¹

2017

JED

View full text Add to dashboard Cite

A Short History of cGMP, Guanylyl Cyclases, and cGMP-Dependent Protein Kinases

Cited by 80 publications

References 119 publications

Phosphodiesterase type-2 and NO-dependentS-nitrosylation mediate the cardioinhibition of the antihypertensive catestatin

Phosphodiesterase type-2 and NO-dependentS-nitrosylation mediate the cardioinhibition of the antihypertensive catestatin

Vasodilator responses to acetylcholine are not mediated by the activation of soluble guanylate cyclase or TRPV4 channels in the rat

Interaction of Cholera Toxin B Subunit with Intestinal Epithelial Cells

Contact Info

Product

Resources

About