Purinergic P2Y6 receptors: A new therapeutic target of age-dependent hypertension.
Pharmacol Res
; 120: 51-59, 2017 Jun.
Article
in En
| MEDLINE
| ID: mdl-28336370
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Receptors, Purinergic P2
/
Purinergic P2 Receptor Antagonists
/
Molecular Targeted Therapy
/
Hypertension
/
Antihypertensive Agents
Type of study:
Etiology_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Pharmacol Res
Journal subject:
FARMACOLOGIA
Year:
2017
Type:
Article