Purinergic P2Y receptors: Molecular diversity and implications for treatment of cardiovascular diseases

Akiyuki Nishimura, Caroline Sunggip, Sayaka Oda, Takuro Numaga-Tomita, Tsuda Makoto, Motohiro Nishida

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us understand the physiological and pathological significance of P2YRs in the cardiovascular system. P2YR-mediated biological functions are predominantly activated by mononucleotides released from non-adrenergic, non-cholinergic nerve endings or non-secretory tissues in response to physical stress or cell injury, though recent studies have suggested the occurrence of ligand-independent P2YR function through receptor-receptor interactions (oligomerization) in several biological processes. In this review, we introduce the functions of P2YRs and possible dimerization with G protein-coupled receptors (GPCRs) in the cardiovascular system. We focus especially on the crosstalk between uridine nucleotide-responsive P2Y6R and angiotensin (Ang) II type1 receptor (AT1R) signaling, and introduce our recent finding that the P2Y6R antagonist MRS2578 interrupts heterodimerization between P2Y6R and AT1R, thereby reducing the risk of AT1R-stimulated hypertension in mice. These results strongly suggest that targeting P2Y6R oligomerization could be an effective new strategy to reduce the risk of cardiovascular diseases.

Original languageEnglish
Pages (from-to)113-128
Number of pages16
JournalPharmacology and Therapeutics
Volume180
DOIs
Publication statusPublished - Dec 1 2017

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Purinergic P2Y Receptors
G-Protein-Coupled Receptors
Cardiovascular System
Cardiovascular Diseases
Uracil Nucleotides
Biological Phenomena
Angiotensin Receptors
Nerve Endings
Dimerization
Pharmacology
Ligands
Hypertension
Wounds and Injuries
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Purinergic P2Y receptors : Molecular diversity and implications for treatment of cardiovascular diseases. / Nishimura, Akiyuki; Sunggip, Caroline; Oda, Sayaka; Numaga-Tomita, Takuro; Makoto, Tsuda; Nishida, Motohiro.

In: Pharmacology and Therapeutics, Vol. 180, 01.12.2017, p. 113-128.

Research output: Contribution to journalReview article

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