Navigation Links
Prostacyclin analogs and PDE 5 inhibitors synergistically stimulate ATP release from human RBCs
Date:9/20/2013

Researchers at Saint Louis University School of Medicine have discovered a novel interaction between prostacyclin (PGI2) analogs and phosphodiesterase 5 (PDE5) inhibitors, two groups of drugs used in the treatment of pulmonary arterial hypertension (PAH). They found that, in combination, these drugs stimulate enhanced release of a potent vasodilator adenosine triphosphate (ATP) from human red blood cells (RBCs). Their study appears in the September 2013 issue of Experimental Biology and Medicine.

PAH is a chronic disorder characterized by sustained increases in pulmonary vascular resistance leading to pulmonary hypertension and right ventricular heart failure. Although the pathophysiology of PAH is not fully understood, the condition has a poor prognosis in the absence of pharmacological intervention. The major classes of drugs used to treat severe PAH include both PGI2 analogs and PDE5 inhibitors.

It is widely accepted that in vascular smooth muscle cells, PGI2 analogs dilate blood vessels by increasing cyclic adenosine 3',5' mono-phosphate (cAMP) while PDE5 increases cyclic guanosine 3',5' mono-phosphate (cGMP) by inhibiting its breakdown. However, human erythrocytes also express functional prostacyclin receptors (IPRs) and possess PDE5. The binding of PGI2 analogs to the erythrocyte IPR activates a well-defined signaling pathway that stimulates increases in cAMP and culminates in the release of the vasoactive molecule, adenosine 3'5' triphosphate (ATP). When released from circulating erythrocytes in the vascular lumen, ATP binds to receptors on the endothelium of pulmonary vessels resulting in the synthesis of vasodilators. Importantly, the levels of cAMP in the erythrocyte IPR signaling pathway are regulated by PDE3, a PDE that is inhibited by cGMP. Levels of cGMP in erythrocytes are regulated by PDE5.

Dr. Randy Sprague, senior author of this article, said "We hypothesized that increases in cGMP resulting from PDE5 inhibition would prevent the breakdown of IPR-mediated increases in cAMP leading to enhanced ATP release. The major finding of this study is that either of two chemically dissimilar inhibitors of PDE5 augment increases in cAMP and ATP release produced by incubation of erythrocytes with an IPR agonist, UT-15C (treprostinil). Dr. Stephanie Knebel, first author, said "Our results demonstrate a new role for both prostacyclin analogs and PDE5 inhibitors in the regulation of IPR-mediated increases in cAMP and ATP release from human erythrocytes." These findings have implications for the development of new therapeutic approaches to the treatment of conditions such as pulmonary arterial hypertension.

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said "This intriguing study by Knebel et al has demonstrated that both PDE5 inhibitors and prostacyclin analogs are involved in the prostacyclin receptor dependent release of cAMP and ATP for human RBCs. Their results suggest new therapeutic approaches for the treatment of pulmonary arterial hypertension".


'/>"/>

Contact: Stephanie M. Knebel
knebelsm@slu.edu
Society for Experimental Biology and Medicine
Source:Eurekalert

Related medicine news :

1. Possible predictive biomarker for patients who may respond to autophagy inhibitors
2. Agios research demonstrates the effects of mutant IDH1 and IDH2 inhibitors in primary tumor models
3. Cisplatin-resistant cancer cells sensitive to experimental anticancer drugs, PARP inhibitors
4. Biomarker may identify neuroblastomas with sensitivity to BET bromodomain inhibitors
5. Researchers use new molecular inhibitors to successfully hit difficult cancer target
6. New mechanism of action for PARP inhibitors discovered
7. PARP inhibitors may have clinical utility in HER2-positive breast cancers
8. Preclinical data support ongoing clinical trials testing IDO inhibitors as a treatment for cancer
9. Inhibitors of shuttle molecule show promise in acute leukemia
10. Fountain Valley, CA Gum Disease Treatment with Dr. Robert Mokbel Now Utilizes the FDA-cleared Laser to Stimulate Bone Growth and Can Prevent Tooth Loss
11. Fort Worth Dental Now Offers Laser Gum Disease Treatment to Stimulate Bone Regrowth and Possibly Save Natural Teeth
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... ... TherapySites, the leading website and online marketing ... Association. This new relationship allows TherapySites to continue to extend their online ... and promotional offers. , "TCA is extremely excited about this new partnership, as ...
(Date:6/27/2016)... ... ... TopConsumerReviews.com recently awarded their highest five-star rating to Best Buy Eyeglasses, an ... United States and Canada wear eyeglasses. Once considered to be a purely functional part ... fashion statement. Even celebrities use glasses as a way of creating an iconic image—like ...
(Date:6/26/2016)... ... June 26, 2016 , ... Pixel Film Studios Released ProSlice Levels, ... editors can give their videos a whole new perspective by using the title ... Pixel Film Studios. , ProSlice Levels contains over 30 Different presets to choose ...
(Date:6/26/2016)... ... June 26, 2016 , ... Many women are confused ... endometriosis. These women need a treatment plan to not only alleviate symptoms and ... help for preservation of fertility and ultimately achieving a pregnancy. The specialists at ...
(Date:6/25/2016)... ... , ... The temporary closing of Bruton Memorial Library on June 21 due to a possible ... often overlooked aspect of head lice: the parasite’s ability to live away from a human ... but a necessary one in the event that lice have simply gotten out of control. ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... -- , , , WHEN: , ... , , , LOCATION: , , , Online, with free ... EXPERT PANELISTS:  , , , Frost & Sullivan,s Global Vice President ... Industry Analyst, Divyaa Ravishankar and Unmesh Lal, Program Manager , ... is witnessing an exceptional era. Several new demand spaces, such as ...
(Date:6/23/2016)... , June 23, 2016  Guerbet announced today ... Inc.,s Supplier Horizon Award . One ... Guerbet was recognized for its support of Premier members ... through clinical excellence, and commitment to lower costs. ... receive this recognition of our outstanding customer service from ...
(Date:6/23/2016)... -- The Biotechnology industry might still be ... opportunities to investors. Stock-Callers.com assesses the recent performances of ... XON ), Vertex Pharmaceuticals Inc. (NASDAQ: ... ), and Regeneron Pharmaceuticals Inc. (NASDAQ: REGN ... complimentary trade alerts at: http://stock-callers.com/registration ...
Breaking Medicine Technology: