|
KMID : 0811720220260020125
|
|
Korean Journal of Physiology & Pharmacology
2022 Volume.26 No. 2 p.125 ~ p.133
|
|
|
Carbon monoxide releasing molecule-2 suppresses stretch-activated atrial natriuretic peptide secretion by activating large-conductance calcium-activated potassium channels
|
|
Li Weijian
Lee Sun-Hwa
Kim Suhn-Hee
|
|
|
Abstract
|
|
|
|
Carbon monoxide (CO) is a known gaseous bioactive substance found across a wide array of body systems. The administration of low concentrations of CO has been found to exert an anti-inflammatory, anti-apoptotic, anti-hypertensive, and vaso-dilatory effect. To date, however, it has remained unknown whether CO influences atrial natriuretic peptide (ANP) secretion. This study explores the effect of CO on ANP secretion and its associated signaling pathway using isolated beating rat atria. Atrial perfusate was collected for 10 min for use as a control, after which high atrial stretch was induced by increasing the height of the outflow catheter. Carbon monoxide releasing molecule-2 (CORM-2; 10, 50, 100 μM) and hemin (HO-1 inducer; 0.1, 1, 50 μM), but not CORM-3 (10, 50, 100 μM), decreased high stretch-induced ANP secretion. However, zinc porphyrin (HO-1 inhibitor) did not affect ANP secretion. The order of potency for the suppression of ANP secretion was found to be hemin > CORM-2 >> CORM-3. The suppression of ANP secretion by CORM-2 was attenuated by pretreatment with 5-hydroxydecanoic acid, paxilline, and 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one, but not by diltiazem, wortmannin, LY-294002, or NG-nitro-L-arginine methyl ester. Hypoxic conditions attenuated the suppressive effect of CORM-2 on ANP secretion. In sum, these results suggest that CORM-2 suppresses ANP secretion via mitochondrial KATP channels and large conductance Ca2+-activated K+ channels.
|
|
|
KEYWORD
|
|
|
ANP, BKCa channel, Carbon monoxide, CORM-2, Hypoxia, KATP channel
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
  
|
|