The research progress of P2Y receptors and its antagonists in cardiovascular diseases / 中国药理学通报

ADP receptors on platelets are mainly divided into two categories: P2X and P2Y. The activation of P2Y receptor is closely related to the occurrence and development of cardiovascular diseases. It plays an important role in regulating platelet activation and aggregation, vascular inflammation, thrombosis and so on. It is the target of ADP receptor blockers. This kind of drugs is also a hot spot in the research and development of antiplatelet drugs. This article reviews the role of P2Y receptor in the occurrence and development of cardiovascular diseases, in order to provide new ideas and reference for the application of P2Y receptor antagonists in the treatment of cardiovascular diseases.

Padronização da triagem de alto desempenho de antagonistas para receptores purinérgicos ativados por UTP a partir da mensuração de cálcio intracelular / Standardization of the screening of high performance antagonists For receivers purinergic activated by UTP from Measurement of calcium intracellular

Os receptores purinérgicos são proteínas expressas na membrana plasmática de diversos tiposcelulares e são ativadas por purinas e pirimidinas extracelulares. Eles são classificados emreceptores P1 e P2, de acordo com o tipo de ligante fisiológico, entretanto, os P2R são aindasubdivididos nas classes: P2XR, que abrange os subtipos ionotrópicos e P2YR, que agrupa ossubtipos acoplados à proteína G. Dentre os P2YR, os subtipos P2Y2 e P2Y4 vem sendoamplamente estudados em virtude de suas funções sobre diversos sistemas biológicos. Umavez ativados pelo UTP, estes receptores promovem a ativação e inibição de canais iônicos,controlam o fluxo de íons através da membrana, induzem um aumento de cálcio intracelular,além de estimular a proliferação celular. Em vista disso, muitos grupos de pesquisa já vemestudando o P2Y2 e o P2Y4 como alvos terapêuticos para o tratamento de diversas doenças,tais como fibrose cística, doença do olho seco, doença de Alzheimer, entre outras. Entretanto,a escassez de moléculas com propriedade antagonista seletiva sobre estes receptores dificultao avanço da caracterização de novos papéis funcionais associados a eles, e neste contexto, osprodutos naturais podem atuar como uma importante fonte para a descoberta de compostosque apresentem a característica almejada. Por isso, o objetivo deste trabalho foi padronizaruma metodologia de mensuração de cálcio intracelular induzido pelo UTP em células dalinhagem de macrófagos murinos J774.G8 e realizar a triagem de extratos oriundos deprodutos naturais a fim de identificar compostos com atividade antagonista sobre o P2Y2R eo P2Y4R. Para isso, foi padronizado um protocolo de carregamento celular com o indicadorde cálcio Fluo-4AM com posterior leitura dos sinais de cálcio no FlexStation III em células J774.G8...

The purinergic receptors are proteins expressed in plasma membrane of many cell types thatare activated by extracellular purines and pyrimidines. They are classified in P1 and P2receptors, according to physiological ligand. However, the P2R are further subdivided in twoclasses: P2X for ionotropic subtypes and P2Y for G-protein coupled ones. Among P2YR, theP2Y2 and P2Y4 subtypes has been widely studied due to their functions in many biologicalsystems. Once activated by UTP, these receptors promote the activation and inhibition of ionchannels, control the flow of ions through the membrane, induce an increase of intracellularcalcium and stimulate the cell proliferation. In view of this, many research groups have beenstudying the P2Y2 and P2Y4 as therapeutic targets for the treatment of several diseases likeCystic Fibrosis, Dry Eye Disease, Alzheimer, among others. However, the lack of moleculeswith selective antagonist property on these receptors difficults the advancement ofcharacterization of new functional roles associated with them, and in this context, naturalproducts may act as an important source for the discovery of compounds that present thisdesired feature. Therefore, the aim of this study was to standardize a methodology formeasurement of intracellular calcium mobilization induced by UTP in a murine macrophagecell line J774.G8 and perform the screening of extracts derived from natural products in orderto identify compounds with antagonist activity on the P2Y2R and P2Y4R. For this, it wasstandardized a protocol of cell labeling with calcium indicator Fluo-4AM in J774.G8 cellswith subsequent detection of calcium signals in FlexStation III...

Calcium-dependent and -independent mechanisms of P2Y receptor regulated anion secretion in polarized epithelia

No abstract available.