Purinergic P2Y6 receptors: A new therapeutic target of age-dependent hypertension

Caroline Sunggip, Akiyuki Nishimura, Kakeru Shimoda, Takuro Numaga-Tomita, Tsuda Makoto, Motohiro Nishida

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertension, although the control rates remain unsatisfactory especially in the elder patients with hypertension. Purinergic receptors, activated by adenine, uridine nucleotides and nucleotide sugars, play pivotal roles in many biological processes, including platelet aggregation, neurotransmission and hormone release, and regulation of cardiovascular contractility. Since clopidogrel, a selective inhibitor of G protein-coupled purinergic P2Y12 receptor (P2Y12R), achieved clinical success as an anti-platelet drug, P2YRs has been attracted more attention as new therapeutic targets of cardiovascular diseases. We have revealed that UDP-responsive P2Y6R promoted angiotensin type 1 receptor (AT1R)-stimulated vascular remodeling in mice, in an age-dependent manner. Moreover, the age-related formation of heterodimer between AT1R and P2Y6R was disrupted by MRS2578, a P2Y6R-selective inhibitor. These findings suggest that P2Y6R is a therapeutic target to prevent age-related hypertension.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalPharmacological Research
Volume120
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

Purinergic Receptors
Hypertension
Angiotensin Type 1 Receptor
clopidogrel
Purinergic P2Y12 Receptors
Uracil Nucleotides
Biological Phenomena
Uridine Diphosphate
Adenine Nucleotides
Therapeutics
Renin-Angiotensin System
Platelet Aggregation
GTP-Binding Proteins
Synaptic Transmission
Homeostasis
Cardiovascular Diseases
Blood Platelets
Nucleotides
Hormones
purinoceptor P2Y6

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Purinergic P2Y6 receptors : A new therapeutic target of age-dependent hypertension. / Sunggip, Caroline; Nishimura, Akiyuki; Shimoda, Kakeru; Numaga-Tomita, Takuro; Makoto, Tsuda; Nishida, Motohiro.

In: Pharmacological Research, Vol. 120, 01.06.2017, p. 51-59.

Research output: Contribution to journalReview article

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