scholarly journals The Role and Molecular Mechanism of P2Y12 Receptors in the Pathogenesis of Atherosclerotic Cardiovascular Diseases

2021 ◽  
Vol 11 (19) ◽  
pp. 9078
Author(s):  
Lu Wang ◽  
Jinxuan Wang ◽  
Jianxiong Xu ◽  
Weixi Qin ◽  
Yuming Wang ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Molecular Mechanism ◽  
Morphological Changes ◽  
Adenosine Diphosphate ◽  
P2y12 Receptor ◽  
Uridine Diphosphate ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Signal Transductions ◽  
G Protein Coupled ◽  
Receptor Family

The P2Y receptor family is a class of G protein-coupled receptors activated primarily by adenosine triphosphate (ATP), adenosine diphosphate (ADP), uridine triphosphate (UTP) and uridine diphosphate (UDP). The P2Y12 receptor is expressed on platelets which mediates platelet aggregation and morphological changes. At the same time, during the process of vascular remodeling and atherosclerosis, ADP can also promote the migration and proliferation of vascular smooth muscle and endothelial cells through P2Y12 receptor activating. Furthermore, P2Y12 is involved in many signal transductions processes, such as intimal hyperplasia, monocyte infiltration and so on, which play an important role in immune inflammation and brain injury. In order to solve the diseases induced by P2Y12 receptor, inhibitors such as ticagrelor, clopidogrel were widely used for cardiovascular diseases. However, there were some problems, such as limited antithrombotic effect, remain unsolved. This article summarizes the role and molecular mechanism of P2Y12 receptors in the pathogenesis of cardiovascular-related diseases, providing in-depth expounding on the molecular mechanism of P2Y12 receptor inhibitors and contributing to the treatment of diseases based on P2Y12 receptors.

Mode of action of P2Y12 antagonists as inhibitors of platelet function

2011 ◽  
Vol 105 (01) ◽  
pp. 96-106 ◽  
Author(s):  
Jackie Glenn ◽  
Ann White ◽  
Sue Fox ◽  
Hans van Giezen ◽  
Sven Nylander ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
G Protein ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
P2y12 Receptor ◽  
Receptor Antagonists ◽  
Receptor Agonists ◽  
P2y12 Antagonists ◽  
Induced Aggregation ◽  
G Protein Coupled

SummaryP2Y12 receptor antagonists are antithrombotic agents that inhibit platelet function by blocking the effects of adenosine diphosphate (ADP) at P2Y12 receptors. However, some P2Y12 receptor antagonists may affect platelet function through additional mechanisms. It was the objective of this study to investigate the possibility that P2Y12 antagonists inhibit platelet function through interaction with G-protein-coupled receptors other than P2Y12 receptors. We compared the effects of cangrelor, ticagrelor and the prasugrel active metabolite on platelet aggregation and on phosphorylation of vasodilator-stimulated phosphoprotein (VASP). We compared their effects with those of selective IP, EP4 and A2A agonists, which act at Gs-coupled receptors. All three P2Y12 antagonists were strong inhibitors of ADP-induced platelet aggregation but only partial inhibitors of aggregation induced by thrombin receptor activating peptide (TRAP) or the thromboxane A2 mimetic U46619. Further, after removing ADP and its metabolites using apyrase and adenosine deaminase, the P2Y12 antagonists produced only minor additional inhibition of TRAP or U46619-induced aggregation. Conversely, the Gs-coupled receptor agonists always produced strong inhibition of aggregation irrespective of whether ADP was removed. Other experiments using selective receptor agonists and antagonists provided no evidence of any of the P2Y12 antagonists acting through PAR1, TP, IP, EP4, A2A or EP3 receptors. All three P2Y12 antagonists enhanced VASPphosphorylation to a small and equal extent but the effects were much smaller than those of the IP, EP4 and A2A agonists. The effects of cangrelor, ticagrelor and prasugrel on platelet function are mediated mainly through P2Y12 receptors and not through another G-protein-coupled receptor.

scholarly journals Platelet Purinergic Receptors in Thrombosis and Inflammation

2020 ◽  
Vol 40 (02) ◽  
pp. 145-152 ◽  
Author(s):  
Christian Gachet ◽  
Beatrice Hechler
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Adenosine Diphosphate ◽  
Specific Role ◽  
Uridine Diphosphate ◽  
Dense Granules ◽  
Acute Responses ◽  
Inflammatory Processes ◽  
Diphosphate Glucose ◽  
G Protein Coupled

AbstractIt took approximately 40 years from the seminal identification of adenosine diphosphate (ADP) as the factor R, an agent derived from red blood cells inducing platelet adhesion to glass, to the completion of the repertoire of its receptors on platelets and its importance in haemostasis and thrombosis. ADP, either derived from red blood cells or released by platelets themselves, stimulates platelets via two G protein-coupled receptors, P2Y1 and P2Y12. In addition, adenosine triphosphate, also contained in the platelet dense granules, activates the P2X1 cation channel. Each of these receptors plays a specific role during platelet activation and aggregation, with relevance to haemostasis, thrombosis and various inflammatory processes where platelets are involved including chronic responses such as atherosclerosis or acute responses such as sepsis, endotoxaemia or allergic asthma. Finally, platelets also express P2Y14, a receptor activated by released uridine diphosphate glucose. Although devoid of any known role in haemostasis, this receptor seems to play a specific role in neutrophil chemotaxis.

Cumulative prevalence of risk factors for atherosclerotic cardiovascular diseases in Iranian adolescents: IHHP-HHPC

2005 ◽  
Vol 81 (6) ◽  
pp. 447-453 ◽  
Author(s):  
Roya Kelishadi ◽  
Gholamhossein Sadri ◽  
Ali Akbar Tavasoli ◽  
Manijeh Kahbazi ◽  
Hamid Reza Roohafza ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Cumulative Prevalence

scholarly journals Resveratrol Protects Cardiac Tissue in Experimental Malignant Hypertension Due to Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Properties

2021 ◽  
Vol 22 (9) ◽  
pp. 5006
Author(s):  
Jelica Grujić-Milanović ◽  
Vesna Jaćević ◽  
Zoran Miloradović ◽  
Djurdjica Jovović ◽  
Ivica Milosavljević ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Diseases ◽  
Cardiac Tissue ◽  
Morphological Changes ◽  
Chronic Administration ◽  
Heart Tissue ◽  
Severe Form ◽  
Malignant Hypertension ◽  
Experimental Hypertension ◽  
Resveratrol Treatment

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.

scholarly journals Adhesion GPCRs in Glioblastoma

2021 ◽  
Author(s):  
Gabriele Stephan ◽  
Niklas Ravn-Boess ◽  
Dimitris G Placantonakis
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptors ◽  
The Past ◽  
Novel Treatment ◽  
The Family ◽  
Health And Disease ◽  
Basic Biology ◽  
G Protein Coupled ◽  
Potential Use ◽  
Receptor Family

Abstract Members of the adhesion family of G protein-coupled receptors (GPCRs) have received attention for their roles in health and disease, including cancer. Over the past decade, several members of the family have been implicated in the pathogenesis of glioblastoma. Here, we discuss the basic biology of adhesion GPCRs and review in detail specific members of the receptor family with known functions in glioblastoma. Finally, we discuss the potential use of adhesion GPCRs as novel treatment targets in neuro-oncology.

scholarly journals Characterization of the G protein-coupled receptor family SREB across fish evolution

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Timothy S. Breton ◽  
William G. B. Sampson ◽  
Benjamin Clifford ◽  
Anyssa M. Phaneuf ◽  
Ilze Smidt ◽  
...  
Keyword(s):  
G Protein ◽  
Genomic Structure ◽  
Integrated Approach ◽  
Orphan Receptor ◽  
Specific Gene ◽  
Testicular Development ◽  
Brain Expression ◽  
And Function ◽  
G Protein Coupled ◽  
Receptor Family

AbstractThe SREB (Super-conserved Receptors Expressed in Brain) family of G protein-coupled receptors is highly conserved across vertebrates and consists of three members: SREB1 (orphan receptor GPR27), SREB2 (GPR85), and SREB3 (GPR173). Ligands for these receptors are largely unknown or only recently identified, and functions for all three are still beginning to be understood, including roles in glucose homeostasis, neurogenesis, and hypothalamic control of reproduction. In addition to the brain, all three are expressed in gonads, but relatively few studies have focused on this, especially in non-mammalian models or in an integrated approach across the entire receptor family. The purpose of this study was to more fully characterize sreb genes in fish, using comparative genomics and gonadal expression analyses in five diverse ray-finned (Actinopterygii) species across evolution. Several unique characteristics were identified in fish, including: (1) a novel, fourth euteleost-specific gene (sreb3b or gpr173b) that likely emerged from a copy of sreb3 in a separate event after the teleost whole genome duplication, (2) sreb3a gene loss in Order Cyprinodontiformes, and (3) expression differences between a gar species and teleosts. Overall, gonadal patterns suggested an important role for all sreb genes in teleost testicular development, while gar were characterized by greater ovarian expression that may reflect similar roles to mammals. The novel sreb3b gene was also characterized by several unique features, including divergent but highly conserved amino acid positions, and elevated brain expression in puffer (Dichotomyctere nigroviridis) that more closely matched sreb2, not sreb3a. These results demonstrate that SREBs may differ among vertebrates in genomic structure and function, and more research is needed to better understand these roles in fish.

scholarly journals A Molecular Mechanism for Sequential Activation of a G Protein-Coupled Receptor

2016 ◽  
Vol 23 (3) ◽  
pp. 392-403 ◽  
Author(s):  
Manuel Grundmann ◽  
Irina G. Tikhonova ◽  
Brian D. Hudson ◽  
Nicola J. Smith ◽  
Klaus Mohr ◽  
...  
Keyword(s):  
G Protein ◽  
Molecular Mechanism ◽  
G Protein Coupled Receptor ◽  
Sequential Activation ◽  
G Protein Coupled

Aprotinin: is it prothrombotic?

Perfusion ◽  
2001 ◽  
Vol 16 (5) ◽  
pp. 401-409 ◽  
Author(s):  
M Poullis ◽  
R C Landis ◽  
K M Taylor
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Mechanism Of Action ◽  
Adenosine Diphosphate ◽  
Platelet Membrane ◽  
Calcium Flux ◽  
Thrombin Receptor ◽  
Proteolytic Activation ◽  
Agonist Peptide ◽  
Receptor Family

Controversy continues as to whether aprotinin (Trasylol) is prothrombotic. The recent discovery of the thrombin receptor family, known as the protease-activated receptor family (PAR) has been essential in aiding our understanding of the mechanism of action of aprotinin. Our results show that aprotinin has no effect on platelet aggregation induced by adrenaline, adenosine diphosphate, phorbol-12-myristate-13-acetate, collagen or PAR 1 agonist peptide. However, aprotinin inhibits thrombin-induced platelet activation as assessed by macroaggregation, microaggregation and platelet membrane calcium flux. Aprotinin inhibits proteolytic activation of platelets, but platelets can still be activated by non-proteolytic mechanisms.

scholarly journals Generating FSH antagonists and agonists through immunization against FSH receptor N-terminal decapeptides

1999 ◽  
Vol 22 (2) ◽  
pp. 151-159 ◽  
Author(s):  
L Abdennebi ◽  
L Couture ◽  
D Grebert ◽  
E Pajot ◽  
R Salesse ◽  
...  
Keyword(s):  
Chinese Hamster ◽  
Biochemical Properties ◽  
Ovary Cell ◽  
Fsh Receptor ◽  
Female Mice ◽  
Specific Receptors ◽  
Ovary Cell Line ◽  
G Protein Coupled ◽  
Follicle Maturation ◽  
Receptor Family

Follicle-stimulating hormone (FSH) via interaction with G-protein coupled specific receptors plays a central role in the control of gametogenesis in mammals of both sexes. In females, FSH is crucial for follicle growth, follicle maturation and ovulation. FSH receptors, together with luteinizing hormone-chorionic gonadotropin and thyrotropin receptors belong to a subfamily of structurally related receptors within the seven transmembrane receptor family. Among several other regions, the N-terminus of these receptors is believed to be responsible for important specific hormone-receptor contact sites. Recombinant filamentous phages displaying at their surface three overlapping N-terminal decapeptides of the FSH receptor, peptides A18-27, B25-34 and C29-38 were constructed. Ewes and female mice were immunized against the three FSH receptor (FSHR) recombinant phages. Immunoglobulins purified from immunized animals were analyzed for their biochemical properties on a Chinese hamster ovary cell line expressing the porcine FSH receptor. AntiA and antiB immunoglobulins (IgGs) behave as antagonists for 125I-FSH binding and for FSH-dependent cAMP production, while antiC IgGs did not compete for hormone binding. By contrast, antibodies against the C29-38 peptide displayed FSH agonist activity and stimulated the FSH receptor, whereas antiA and antiB IgGs did not. Furthermore, when the FSHR phages were used as peptidic vaccines, they induced a reversible inhibition of ovulation rate in ewes, and impaired fertility in female mice.

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