Pharmacogenetics and Pharmacodynamics of Purinergic Drugs

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics".

Deadline for manuscript submissions: closed (20 June 2021) | Viewed by 5483

Special Issue Editors

Faculty of Optics and Optometry and Director of Ocupharm Group Research, Universidad Complutense de Madrid, 28037 Madrid, Spain
Interests: dry eye; myopia; contact lenses; ocular biochemistry; glaucoma
Special Issues, Collections and Topics in MDPI journals
R&D Department Avizor Eye Care Solutions, Ocupharm Research Group, Complutense University, 28037 Madrid, Spain
Interests: melatonin; glaucoma; eye care solutions; dry eye; contact lenses
Special Issues, Collections and Topics in MDPI journals
Biochemistry and Molecular Biology, Veterinary Medicine School, Complutense University, 28037 Madrid, Spain
Interests: purinergic receptors; nucleotides; brain development; neuroprotection; neuroregeneration
Faculty of Optics and Optometry, Ocupharm Group Research, Complutense University, 28037 Madrid, Spain
Interests: nucleotides; purinergic signaling; melatonin; glaucoma; dry eye; contact lenses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nucleotides and dinucleotides are a family of compounds with a central role in metabolism at cellular level. Since the characterization and cloning of purinergic receptors in the early 1990’s there has been an explosion of interest in the physiology and pathophysiology of these nucleotidic compounds.

They have been investigated in relation to a wide variety of pathologies, including neurodegenerative and neurological disorders, cardiovascular, skeletal, reproductive and immune system diseases, as well as alterations in sense organs, airways, skin, muscles, gut, kidney, urinary tract and eye. Furthermore, several purinergic drugs are already on the market, others are being investigated on clinical trials and many more are being explored for therapeutic effects on different conditions.

This Special Issue will be focused on different studies about the interactions of purinergic drugs with genes related with pathologies and about the pharmacodynamics of purinergic receptor agonists and antagonists to treat a wide number of pathologies.

Prof. Dr. Gonzalo Carracedo
Dr. Alejandro Martínez-Åguila
Dr. Rosa Gomez-Villafuertes
Dr. Alba Martín-Gil
Guest Editors

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Keywords

  • nucleotides
  • dinucleotides
  • purinergic agonists
  • purinergic antagonists
  • pharmacodynamics
  • pharmacogenetics
  • purinergic signaling

Published Papers (2 papers)

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Research

22 pages, 2396 KiB  
Article
Purinergic P2Y2 and P2X4 Receptors Are Involved in the Epithelial-Mesenchymal Transition and Metastatic Potential of Gastric Cancer Derived Cell Lines
by Mauricio Reyna-Jeldes, Erwin De la Fuente-Ortega, Daniela Cerda, Erandi Velázquez-Miranda, Katherine Pinto, Francisco G. Vázquez-Cuevas and Claudio Coddou
Pharmaceutics 2021, 13(8), 1234; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081234 - 11 Aug 2021
Cited by 12 | Viewed by 2700
Abstract
Gastric cancer (GC) is a major health concern worldwide, presenting a complex pathophysiology that has hindered many therapeutic efforts so far. In this context, purinergic signaling emerges as a promising pathway for intervention due to its known role in cancer cell proliferation and [...] Read more.
Gastric cancer (GC) is a major health concern worldwide, presenting a complex pathophysiology that has hindered many therapeutic efforts so far. In this context, purinergic signaling emerges as a promising pathway for intervention due to its known role in cancer cell proliferation and migration. In this work, we explored in more detail the role of purinergic signaling in GC with several experimental approaches. First, we measured extracellular ATP concentrations on GC-derived cell lines (AGS, MKN-45, and MKN-74), finding higher levels of extracellular ATP than those obtained for the non-tumoral gastric cell line GES-1. Next, we established the P2Y2 and P2X4 receptors (P2Y2R and P2X4R) expression profile on these cells and evaluated their role on cell proliferation and migration after applying overexpression and knockdown strategies. In general, a P2Y2R overexpression and P2X4R downregulation pattern were observed on GC cell lines, and when these patterns were modified, concomitant changes in cell viability were observed. These modifications on gene expression also modified transepithelial electrical resistance (TEER), showing that higher P2Y2R levels decreased TEER, and high P2X4R expression had the opposite effect, suggesting that P2Y2R and P2X4R activation could promote and suppress epithelial-mesenchymal transition (EMT), respectively. These effects were confirmed after treating AGS cells with UTP, a P2Y2R-agonist that modified the expression patterns towards mesenchymal markers. To further characterize the effects of P2Y2R activation on EMT, we used cDNA microarrays and observed that UTP induced important transcriptional changes on several cell processes like cell proliferation induction, apoptosis inhibition, cell differentiation induction, and cell adhesion reduction. These results suggest that purinergic signaling plays a complex role in GC pathophysiology, and changes in purinergic balance can trigger tumorigenesis in non-tumoral gastric cells. Full article
(This article belongs to the Special Issue Pharmacogenetics and Pharmacodynamics of Purinergic Drugs)
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16 pages, 2395 KiB  
Article
Chronic Kidney Disease-Induced Arterial Media Calcification in Rats Prevented by Tissue Non-Specific Alkaline Phosphatase Substrate Supplementation Rather Than Inhibition of the Enzyme
by Britt Opdebeeck, Ellen Neven, José Luis Millán, Anthony B. Pinkerton, Patrick C. D’Haese and Anja Verhulst
Pharmaceutics 2021, 13(8), 1138; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081138 - 26 Jul 2021
Cited by 7 | Viewed by 2005
Abstract
Patients with chronic kidney disease (CKD) suffer from arterial media calcification and a disturbed bone metabolism. Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes the calcification inhibitor pyrophosphate (PPi) into inorganic phosphate (Pi) and thereby stimulates arterial media calcification as well as physiological bone mineralization. This [...] Read more.
Patients with chronic kidney disease (CKD) suffer from arterial media calcification and a disturbed bone metabolism. Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes the calcification inhibitor pyrophosphate (PPi) into inorganic phosphate (Pi) and thereby stimulates arterial media calcification as well as physiological bone mineralization. This study investigates whether the TNAP inhibitor SBI-425, PPi or the combination of both inhibit arterial media calcification in an 0.75% adenine rat model of CKD. Treatments started with the induction of CKD, including (i) rats with normal renal function (control diet) treated with vehicle and CKD rats treated with either (ii) vehicle, (iii) 10 mg/kg/day SBI-425, (iv) 120 µmol/kg/day PPi and (v) 120 µmol/kg/day PPi and 10 mg/kg/day SBI-425. All CKD groups developed a stable chronic renal failure reflected by hyperphosphatemia, hypocalcemia and high serum creatinine levels. CKD induced arterial media calcification and bone metabolic defects. All treatments, except for SBI-425 alone, blocked CKD-related arterial media calcification. More important, SBI-425 alone and in combination with PPi increased osteoid area pointing to a less efficient bone mineralization. Clearly, potential side effects on bone mineralization will need to be assessed in any clinical trial aimed at modifying the Pi/PPi ratio in CKD patients who already suffer from a compromised bone status. Full article
(This article belongs to the Special Issue Pharmacogenetics and Pharmacodynamics of Purinergic Drugs)
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