Possible Interaction: Adenosine and Dinoprostone

“Combined PGE2 and adenosine treatment resulted in augmentation of cAMP production, PKA activity, CREB phosphorylation and inhibition of Akt phosphorylation.”

“In contrast, Rp-8-Br-cAMPS, an inhibitor of PKA type I blocked their immunosuppressive effects, suggesting that the inhibitory effects of PGE2 and adenosine are mediated via common pathway with activation of cAMP-PKA and inhibition of Akt.”

“IntroductionWe hypothesize that adenosine and PGE2 could have a complementary immunosuppressive effect that is mediated via common cAMP-PKA signaling.”

“Using agonists and antagonists specific for PGE2 and adenosine receptors we found that cooperation of PGE2 and adenosine in their inhibitory effects are mediated via EP2 and A2A receptors, respectively.”

“Given the uncontrolled inflammatory phenotype observed in knockout mice … in view of the potent inhibitory actions of prostaglandin E2 on inflammatory cells, an increased cyclooxygenase-2 expression resulting from A2A receptor activation, observed particularly … neutrophils, may take part in an early modulatory mechanism promoting anti-inflammatory activities of adenosine.”

“Furosemide, prostaglandins PGE2 and PGI2) and adenosine modulate its function. (”

“It is concluded that adenosine enhances the steroidogenic response by functional bovine luteal cells to hCG, PGE1 or PGE2 and that adenosine reduces the luteolytic response to PGF2 alpha by gonadotropin-stimulated bovine luteal cells in vitro.”

“Secretion of progesterone by day 7 or 13 bovine luteal cells was increased by hCG, PGE1 or PGE2 which was increased further when co-incubated with adenosine (p less than 0.05).”

“ Adenosine has been shown to promote cyclooxygenase-2 activity and prostaglandin E2 ”

“Expert opinion: Pharmacologic blocking of adenosine– PGE2 collaboration provides a clinically-feasible strategy for disarming of Treg.”

“A concomitant inhibition of PGE2 and adenosine via the common intracellular cAMP pathway might be a novel approach for improving results of immune therapies for cancer.”

“The present study demonstrates for the first …-infiltrating lymphocytes (TILs); (2) the combination PGE2 … CADO have additive suppressive effects; and (3) the cooperative immunosuppressive actions of PGE2 and CADO are mediated via …) and T cell receptor (TCR) inhibitor Csk leading to inhibition of Lck, ZAP-70 and Akt phosphorylation. (”

“Production of PGE2 in response to exogenous arachidonic acid was also increased by adenosine and correlated with COX-2 protein levels.”

“Thus, adenosine may promote a self-limiting regulatory process through the increase of PGE2 generation, which may result in the inhibition of PMN functions.”

“The ease with which PGE2 reverses the effects of PGI2, PGD2 and adenosine , but adds to the effects of AH-P 719 and DN-9693, suggests that PDE inhibitors might offer greater potential than these AC stimulators as an anti-thrombotic strategy.(ABSTRACT TRUNCATED AT 250 WORDS)”