Pannexin 1 Channels as an Unexpected New Target of the Anti-Hypertensive Drug Spironolactone.

ABSTRACT: RATIONALE:Resistant hypertension is a major health concern with unknown cause. Spironolactone is an effective antihypertensive drug, especially for patients with resistant hypertension, and is considered by the World Health Organization as an essential medication. Although spironolactone can act at the mineralocorticoid receptor (MR; NR3C2), there is increasing evidence of MR-independent effects of spironolactone. OBJECTIVE:Here, we detail the unexpected discovery that Panx1 (pannexin 1) channels could be a relevant in vivo target of spironolactone. METHODS AND RESULTS:First, we identified spironolactone as a potent inhibitor of Panx1 in an unbiased small molecule screen, which was confirmed by electrophysiological analysis. Next, spironolactone inhibited α-adrenergic vasoconstriction in a

SUBMITTER: Good ME 

PROVIDER: S-EPMC5815904 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature