Current Modulation of Guanylate Cyclase Pathway Activity—Mechanism and Clinical Implications
Abstract
:1. Introduction
2. Guanylate Cyclases
3. NO Production
4. Pharmacological Intervention
4.1. Natriuretic Peptides Analogues
4.2. Inhibition of Neprilysin
4.3. Inhibition of Phosphodiesterases
4.4. Direct Activation of Soluble Guanylate Cyclase
5. Conclusions and Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviation
cAMP | Cyclic Adenosine Monophosphate |
CO | carbon monoxide |
FDA | US Food and Drug Administration |
GC | guanylate cyclase |
GC-A | guanylate cyclase type A |
GC-B | guanylate cyclase type B |
GC-C | guanylate cyclase type C |
GC-D | guanylate cyclase type D |
GC-E | guanylate cyclase type E |
GC-F | guanylate cyclase type F |
GC-G | guanylate cyclase type G |
sGC | soluble guanylate cyclase |
mGC | guanylate cyclase-coupled receptor or membrane-bound guanylyl cyclase |
GMP | guanosine monophosphate |
cGMP | cyclic guanosine monophosphate |
GTP | guanosine triphosphate |
LPS | lipopolysaccharide/endotoxin |
NP | natriuretic peptide |
ANP | natriuretic peptide type A |
BNP | natriuretic peptide type B |
CNP | natriuretic peptide type C |
NANC | non-adrenergic, non-cholinergic |
NEP | neprilysin |
NO | nitric oxide |
NOS | nitric oxide synthase |
NOS-1 | neuronal nitric oxide synthase |
NOS-2 | cytokine-inducible nitric oxide synthase |
NOS-3 | endothelial nitric oxide synthase |
PAH | pulmonary arterial hypertension |
PDE5 | Phosphodiesterase type 5 |
PDE9 | Phosphodiesterase type 9 |
PKG | cGMP dependent protein kinase G |
SNP | sodium nitroprusside |
TNFα | tumor necrosis factor α |
NT-proBNP | N-terminal pro-brain natriuretic peptide |
VASP | vasodilator-stimulated phosphoprotein |
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Guanylyl Cyclase | Tissue Expression | Physiological Activator | Key Effects |
---|---|---|---|
Soluble α1 | Cardiovascular system, platelets, brain | NO, CO | Vasodilation, angiogenesis, inhibition of platelet aggregation |
Soluble α2 | Cardiovascular system, brain | NO, CO | Vasodilation, angiogenesis |
Soluble β1 | Cardiovascular system, platelets, brain | NO, CO | Vasodilation, angiogenesis inhibition of platelet aggregation, intestinal motility |
Soluble β2 | Gastrointestinal tract, liver, kidney | NO, CO | Apoptosis, inhibition of anti-apoptotic endothelin pathway |
GC-A | Cardiovascular system (vascular smooth muscle, heart), lung, kidney, adrenal, adipose tissue | ANP, BNP | Vasodilation, angiogenesis, regulation of hypertrophy, remodeling processes |
GC-B | Cardiovascular system (vascular smooth muscle, endothelium, heart), lung, bone, brain, liver, uterus, follicle | CNP | Vasodilation, angiogenesis. regulation of hypertrophy, remodeling processes, cartilage homeostasis and endochondral bone formation, regulation of female fertility |
GC-C | Intestinal epithelium | Guanylin, uroguanylin and bacterial heat-stable enterotoxin | Regulation of colonic epithelial cell proliferation |
GC-D | Olfactory bulb | Guanylin, uroguanylin, CO2/HCO3 | guanylin- and uroguanylin-dependent olfactory signaling, food and odor preference response (mices) |
GC-E | Retina, pineal gland | guanylyl cyclase activator proteins | Vision process |
GC-F | Retina | guanylyl cyclase activator proteins | Vision process |
GC-G | Olfactory bulb, lung, intestine, skeletal muscle, testes | Pheromones, CO2/HCO3 | detection of the volatile alarm pheromones, kidney, ischemia/reperfusion preconditioning |
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Grześk, G.; Nowaczyk, A. Current Modulation of Guanylate Cyclase Pathway Activity—Mechanism and Clinical Implications. Molecules 2021, 26, 3418. https://doi.org/10.3390/molecules26113418
Grześk G, Nowaczyk A. Current Modulation of Guanylate Cyclase Pathway Activity—Mechanism and Clinical Implications. Molecules. 2021; 26(11):3418. https://doi.org/10.3390/molecules26113418
Chicago/Turabian StyleGrześk, Grzegorz, and Alicja Nowaczyk. 2021. "Current Modulation of Guanylate Cyclase Pathway Activity—Mechanism and Clinical Implications" Molecules 26, no. 11: 3418. https://doi.org/10.3390/molecules26113418