Adenosine and preeclampsia

Abstract

Adenosine is an endogenous nucleoside with pleiotropic effects in different physiological processes including circulation, renal blood flow, immune function, or glucose homeostasis. Changes in adenosine membrane transporters, adenosine receptors, and corresponding intracellular signalling network associate with development of pathologies of pregnancy, including preeclampsia. Preeclampsia is a cause of maternal and perinatal morbidity and mortality affecting 3-5% of pregnancies. Since the proposed mechanisms of preeclampsia development include adenosine-dependent biological effects, adenosine membrane transporters and receptors, and the associated signalling mechanisms might play a role in the pathophysiology of preeclampsia. Preeclampsia associates with increased adenosine concentration in the maternal blood and placental tissue, likely due to local hypoxia and ischemia (although not directly demonstrated), microthrombosis, increased catecholamine release, and platelet activation. In addition, abnormal expression and function of equilibrative nucleoside transporters is described in foetoplacental tissues from preeclampsia; however, the role of adenosine receptors in the aetiology of this disease is not well understood. Adenosine receptors activation may be related to abnormal trophoblast invasion, angiogenesis, and ischemia/reperfusion mechanisms in the placenta from preeclampsia. These mechanisms may explain only a low fraction of the associated abnormal transformation of spiral arteries in preeclampsia, triggering cellular stress and inflammatory mediators release from the placenta to the maternal circulation. Although increased adenosine concentration in preeclampsia may be a compensatory or adaptive mechanism favouring placental angiogenesis, a poor angiogenic state is found in preeclampsia. Thus, preeclampsia-associated complications might affect the cell response to adenosine due to altered expression and activity of adenosine receptors, membrane transporters, or cell signalling mechanisms. This review summarizes the evidence available on the potential involvement of the adenosine in the clinical, pathophysiology, and therapeutic features of preeclampsia.

Intracellular acidification increases adenosine transport in human umbilical vein endothelial cells

“…Since the broad biological actions of adenosine in the human body [5], including the foetoplacental vasculature [3,5,9,11,12,[33][34][35], changes in the capacity of the endothelium to 285 remove this nucleoside from the extracellular space is crucial. Our results may have M A N U S C R I P T…”

“…Thus, GDM could potentially associate with acidic pHo resulting from increased H + efflux leading to intracellular alkalization as reported in cancer cells [2,3,17]. However, there is not available information regarding changes in pHi and hENT1 and hENT2 activity in GDM or hyperglycaemia [2,3,34]. Therefore, since hENT1 and hENT2-mediated adenosine transport is increased by acidic pHi, looking for a therapeutic approach to restoring a 295 physiological pHi/pHo ratio, perhaps involving restoration of proper H + efflux via NHE1 …”

Therapeutic potency of pharmacological adenosine receptor agonist/antagonist in angiogenesis, current status and perspectives

“…It is known that A1 and A3 ARs are coupled to Gi/o proteins. Hence, activation of A1 and A3 ARs inhibits adenylyl cyclase activity, cyclic‐AMP (cAMP) production and subsequent protein kinase A (PKA) activity . In contrast, A2a and A2b ARs are coupled to Gs proteins.…”

“…Hence, activation of A1 and A3 ARs inhibits adenylyl cyclase activity, cyclic-AMP (cAMP) production and subsequent protein kinase A (PKA) activity. [16] In contrast, A2a and A2b ARs are coupled to Gs proteins. Activation of A2 subtypes, A2a and A2b, stimulate adenylyl cyclase activity and enhance cAMP concentration followed by sharp increase in PKA activity.…”

Development of a fast CE method for high throughput screening of ecto‐5′‐nucleotidase inhibitors

“…Over expression of ecto‐5’‐nucleotidase leads to enhanced concentration of adenosine in extracellular environment which affects a number of biological processes. Variations in adenosine receptors, adenosine membrane transporters, and corresponding intracellular signaling networks are also reported to be associated with development of preeclampsia . Ecto‐5′‐nucleotidase is reported to be over expressed on many cancer types including thyroid, ovarian, breast, prostate, leukemia, bladder, gastric, eosophageal, and colon cancer .…”