Remote intrathecal morphine preconditioning confers cardioprotection via spinal cord nitric oxide/cyclic guanosine monophosphate/protein kinase G pathway

2015 ◽  
Vol 193 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Yao Lu ◽  
Jun Hu ◽  
Ye Zhang ◽  
Chun Shan Dong ◽  
Gordon Tin Chun Wong
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Protein Kinase ◽  
Intrathecal Morphine ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Protein Kinase G

scholarly journals Nitric Oxide-cGMP Signaling in Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1055-1068
Author(s):  
Ehsan Ataei Ataabadi ◽  
Keivan Golshiri ◽  
Annika Jüttner ◽  
Guido Krenning ◽  
A.H. Jan Danser ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Drug Targets ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Protein Kinase G ◽  
Current Status ◽  
Systemic Hypertension ◽  
Pharmacological Intervention ◽  
Cgmp Signaling

For the treatment of systemic hypertension, pharmacological intervention in nitric oxide-cyclic guanosine monophosphate signaling is a well-explored but unexploited option. In this review, we present the identified drug targets, including oxidases, mitochondria, soluble guanylyl cyclase, phosphodiesterase 1 and 5, and protein kinase G, important compounds that modulate them, and the current status of (pre)clinical development. The mode of action of these compounds is discussed, and based upon this, the clinical opportunities. We conclude that drugs that directly target the enzymes of the nitric oxide-cyclic guanosine monophosphate cascade are currently the most promising compounds, but that none of these compounds is under investigation as a treatment option for systemic hypertension.

scholarly journals Possible Participation of Nitric Oxide/Cyclic Guanosine Monophosphate/Protein Kinase C/ATP-Sensitive K+ Channels Pathway in the Systemic Antinociception of Flavokawin B

2011 ◽  
Vol 108 (6) ◽  
pp. 400-405 ◽  
Author(s):  
Azam Shah Mohamad ◽  
Muhammad Nadeem Akhtar ◽  
Shaik Ibrahim Khalivulla ◽  
Enoch Kumar Perimal ◽  
Mohamed Hanief Khalid ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
K Channels ◽  
Kinase C

scholarly journals P2Y Purinergic Regulation of the Glycine Neurotransmitter Transporters

2011 ◽  
Vol 286 (12) ◽  
pp. 10712-10724 ◽  
Author(s):  
Esperanza Jiménez ◽  
Francisco Zafra ◽  
Raquel Pérez-Sen ◽  
Esmerilda G. Delicado ◽  
Maria Teresa Miras-Portugal ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Synaptic Cleft ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Neuronal Cultures ◽  
Primary Neuronal Cultures ◽  
Neurotransmitter Transporters ◽  
Stimulation Of

The sodium- and chloride-coupled glycine neurotransmitter transporters (GLYTs) control the availability of glycine at glycine-mediated synapses. The mainly glial GLYT1 is the key regulator of the glycine levels in glycinergic and glutamatergic pathways, whereas the neuronal GLYT2 is involved in the recycling of synaptic glycine from the inhibitory synaptic cleft. In this study, we report that stimulation of P2Y purinergic receptors with 2-methylthioadenosine 5′-diphosphate in rat brainstem/spinal cord primary neuronal cultures and adult rat synaptosomes leads to the inhibition of GLYT2 and the stimulation of GLYT1 by a paracrine regulation. These effects are mainly mediated by the ADP-preferring subtypes P2Y1 and P2Y13 because the effects are partially reversed by the specific antagonists N6-methyl-2′-deoxyadenosine-3′,5′-bisphosphate and pyridoxal-5′-phosphate-6-azo(2-chloro-5-nitrophenyl)-2,4-disulfonate and are totally blocked by suramin. P2Y12 receptor is additionally involved in GLYT1 stimulation. Using pharmacological approaches and siRNA-mediated protein knockdown methodology, we elucidate the molecular mechanisms of GLYT regulation. Modulation takes place through a signaling cascade involving phospholipase C activation, inositol 1,4,5-trisphosphate production, intracellular Ca2+ mobilization, protein kinase C stimulation, nitric oxide formation, cyclic guanosine monophosphate production, and protein kinase G-I (PKG-I) activation. GLYT1 and GLYT2 are differentially sensitive to NO/cGMP/PKG-I both in brain-derived preparations and in heterologous systems expressing the recombinant transporters and P2Y1 receptor. Sensitivity to 2-methylthioadenosine 5′-diphosphate by GLYT1 and GLYT2 was abolished by small interfering RNA (siRNA)-mediated knockdown of nitric-oxide synthase. Our data may help define the role of GLYTs in nociception and pain sensitization.

Sign in / Sign up

Export Citation Format

Share Document