Comparative Effects of Hydrogen Sulfide-Releasing Compounds on [3H]D-Aspartate Release from Bovine Isolated Retinae

被引:8
作者
Bankhele, Pratik [1 ]
Salvi, Ankita [1 ]
Jamil, Jamal [1 ]
Njie-Mbye, Fatou [2 ]
Ohia, Sunny [2 ]
Opere, Catherine A. [1 ]
机构
[1] Creighton Univ, Sch Pharm & Hlth Profess, Dept Pharm Sci, 2500 Calif Plaza, Omaha, NE 68178 USA
[2] Texas Southern Univ, Dept Pharmaceut & Environm Hlth Sci, Coll Pharm & Hlth Sci, 3100 Cleburne St, Houston, TX 77004 USA
关键词
Retinae; Aspartate; Hydrogen sulfide; Cystathionine beta-synthase; Cystathionine gamma-lyase; K-ATP channels; ARACHIDONIC-ACID METABOLITES; CYSTATHIONINE BETA-SYNTHASE; ISOLATED PORCINE IRIDES; OPEN-ANGLE GLAUCOMA; INHIBITORY-ACTION; SYMPATHETIC NEUROTRANSMISSION; PHARMACOLOGICAL ACTIONS; HOMOCYSTEINE LEVELS; OXIDATIVE STRESS; CHICK RETINA;
D O I
10.1007/s11064-018-2471-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated the pharmacological actions of a slow-releasing H2S donor, GYY 4137; a substrate for the biosynthesis of H2S, l-cysteine and its precursor, N-acetylcysteine on potassium (K+; 50 mM)-evoked [H-3]D-aspartate release from bovine isolated retinae using the Superfusion Method. GYY 4137 (10 nM-10 A mu M), l-cysteine (100 nM-10 A mu M) and N-acetylcysteine (10 A mu M-1 mM) elicited a concentration-dependent decrease in K+-evoked [H-3]D-aspartate release from isolated bovine retinae without affecting basal tritium efflux. At equimolar concentration of 10 A mu M, the rank order of activity was as follows: l-cysteine > GYY 4137 > N-acetylcysteine. A dual inhibitor of the biosynthetic enzymes for H2S, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), amino-oxyacetic acid (AOA; 3 mM) reversed the inhibitory responses caused by GYY 4137, l-cysteine and N-acetylcysteine on K+-evoked [H-3]D-aspartate release. Glibenclamide (300 A mu M), an inhibitor of K-ATP channels blocked the inhibitory action of GYY 4137 and l-cysteine but not that elicited by N-acetylcysteine on K+-induced [H-3]D-aspartate release. The inhibitory effect of GYY 4137 and l-cysteine on K+-evoked [H-3]D-aspartate release was reversed by the non-specific inhibitor of nitric oxide synthase (NOS), l-NAME (300 A mu M). Furthermore, a specific inhibitor of inducible NOS (iNOS), aminoguanidine (10 A mu M) blocked the inhibitory action of l-cysteine on K+-evoked [H-3]D-aspartate release. We conclude that both donors and substrates for H2S production can inhibit amino acid neurotransmission in bovine isolated retinae, an effect that is dependent, at least in part, upon the intramural biosynthesis of this gas, and on the activity of K-ATP channels and NO synthase.
引用
收藏
页码:692 / 701
页数:10
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