scholarly journals Erratum: Corrigendum: Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure

2004 ◽  
Vol 10 (1) ◽  
pp. 105-105
Author(s):  
Mary Tang ◽  
Guang Wang ◽  
Ping Lu ◽  
Richard H Karas ◽  
Mark Aronovitz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
G Protein ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Vascular Smooth Muscle Relaxation

Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure

10.1038/nm958 ◽  
2003 ◽  
Vol 9 (12) ◽  
pp. 1506-1512 ◽  
Author(s):  
Mary Tang ◽  
Guang Wang ◽  
Ping Lu ◽  
Richard H Karas ◽  
Mark Aronovitz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
G Protein ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Vascular Smooth Muscle Relaxation

Interactions between nitroglycerin and endothelium in vascular smooth muscle relaxation

1991 ◽  
Vol 260 (3) ◽  
pp. H698-H701 ◽  
Author(s):  
J. L. Dinerman ◽  
D. L. Lawson ◽  
J. L. Mehta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Cyclic Monophosphate ◽  
The Mean ◽  
Smooth Muscle Relaxant ◽  
Vascular Smooth Muscle Relaxation

To evaluate the role of endothelium in nitroglycerin (NTG)-mediated vascular relaxation, epinephrine-contracted rat thoracic aortic segments with and without intact endothelium were exposed to NTG (10(-10) to 10(-5) M). Aortic segments with intact (endo+, n = 15) and denuded endothelium (endo-, n = 9) exhibited typical NTG-induced relaxation. However, the mean effective concentration of NTG was lower for endo- than for endo+ segments (P less than 0.001). To determine if this phenomenon related to nitric oxide (NO) generation by endothelium, six endo+ segments were treated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO production. These endo+ segments exhibited greater (P less than 0.001) relaxation in response to NTG than the untreated endo+ segments. Oxyhemoglobin, an inhibitor of guanylate cyclase activation, greatly diminished NTG-mediated relaxation of all aortic segments. To determine if the enhanced NTG-mediated relaxation of endo- segments was unique to the guanosine 3',5'-cyclic monophosphate-dependent vasodilator NTG, other endo+ and endo- segments were exposed to adenosine 3',5'-cyclic monophosphate-dependent vasodilator papaverine (10(-8) to 10(-4) M), and no difference in EC50 was noted between endo+ and endo- segments. Thus endothelium attenuates NTG-mediated vasorelaxation, and this attenuation is abolished by inhibition of endothelial NO production with L-NMMA. These observations indicate that endothelium is a dynamic modulator of vascular smooth muscle relaxant effects of NTG. This modulation appears to result from a competitive interaction between endothelial NO and NTG.

scholarly journals Inhibition of Gαi activity by Gβγ is mediated by PI 3-kinase-γ- and cSrc-dependent tyrosine phosphorylation of Gαi and recruitment of RGS12

2014 ◽  
Vol 306 (9) ◽  
pp. G802-G810 ◽  
Author(s):  
Jiean Huang ◽  
Ancy D. Nalli ◽  
Sunila Mahavadi ◽  
Divya P. Kumar ◽  
Karnam S. Murthy
Keyword(s):  
Smooth Muscle ◽  
Tyrosine Phosphorylation ◽  
G Protein ◽  
Muscle Relaxation ◽  
P38 Map Kinase ◽  
Smooth Muscle Relaxation ◽  
Inhibitory Influence ◽  
Protein Signaling ◽  
P21 Activated Kinase ◽  
Δ Opioid Receptor

Others and we have characterized several Gβγ-dependent effectors in smooth muscle, including G protein-coupled receptor kinase 2 (GRK2), PLCβ3, and phosphatidylinositol (PI) 3-kinase-γ, and have identified various signaling targets downstream of PI 3-kinase-γ, including cSrc, integrin-linked kinase, and Rac1-Cdc42/p21-activated kinase/p38 MAP kinase. This study identified a novel mechanism whereby Gβγ acting via PI 3-kinase-γ and cSrc exerts an inhibitory influence on Gαi activity. The Gi2-coupled δ-opioid receptor agonist d-penicillamine ( 2 , 5 )-enkephalin (DPDPE) activated cSrc, stimulated tyrosine phosphorylation of Gαi2, and induced regulator of G protein signaling 12 (RGS12) association; all three events were blocked by PI 3-kinase (LY294002) and cSrc (PP2) inhibitors and by expression of the COOH-terminal sequence of GRK2-(495–689), a Gβγ-scavenging peptide. Inhibition of forskolin-stimulated cAMP and muscle relaxation by DPDPE was augmented by PP2, LY294002 , and a selective PI 3-kinase-γ inhibitor, AS-605420. Expression of tyrosine-deficient (Y69F, Y231F, or Y321F) Gαi2 mutant or knockdown of RGS12 blocked Gαi2 phosphorylation and Gαi2-RGS12 association and caused greater inhibition of cAMP. Parallel studies using somatostatin, cyclopentyl adenosine, or ACh to activate, respectively, Gi1-coupled somatostatin (sstr3) receptors, and Gi3-coupled adenosine A1 or muscarinic m2 receptors elicited cSrc activation, Gαi1 or Gαi3 phosphorylation, Gαi1-RGS12 or Gαi3-RGS12 association, and inhibition of cAMP. Inhibition of cAMP and muscle relaxation was greatly increased by AS-605240 and PP2. The results demonstrate that Gβγ-dependent tyrosine phosphorylation of Gαi1/2/3 by cSrc facilitated recruitment of RGS12, a Gαi-specific RGS protein with a unique phosphotyrosine-binding domain, resulting in rapid deactivation of Gαi and facilitation of smooth muscle relaxation.

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