Premium
Inhibition of nitrergic neurotransmission in the bovine retractor penis muscle by an oxidant stress: effects of superoxide dismutase mimetics
Author(s) -
Mok Josephine S L,
Paisley Karen,
Martin William
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701809
Subject(s) - chemistry , superoxide dismutase , superoxide , biochemistry , cytochrome c , tiron , oxidative stress , enzyme , mitochondrion
A number of superoxide dismutase (SOD) mimetics were examined both biochemically for their ability to inhibit the superoxide‐catalyzed reduction of cytochrome c and nitro blue tetrazolium, and functionally for their ability to mimic authentic Cu/Zn SOD in restoring nitrergic neurotransmission in bovine retractor penis (BRP) muscle following its inhibition by oxidant stress. The SOD mimetics investigated were CuSO 4 , MnCl 2 , CuDIPS (copper [II][diisopropylsalicylate] 2 ), MnTBAP (manganese [III] tetrakis 4‐benzoic acid porphyrin), MnTMPyP (manganese [III] tetrakis 1‐methyl‐4‐pyridyl porphyrin pentachloride), tiron (4,5‐dihydroxy‐1,3‐benzene disulphonic acid), PTIYO (4‐phenyl,2,2,5,5,‐tetramethyl‐3‐imidazolin‐1‐yloxy‐3‐oxide) and tempol (4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐N‐oxyl). The rank order of potency in inhibiting the reduction of cytochrome c was: CuSO 4 MnCl 2 CuDIPSMnTMPyP>MnTBAP>tempoltiron>PTIYO. The requirement for EDTA (0.1 m M ) prevented assessment of the activity of CuSO 4 , MnCl 2 and CuDIPS in the assay involving inhibition of reduction of nitro blue tetrazolium. However, the rank order of potency for those agents which could be examined (MnTMPyP>MnTBAP>tirontempol>PTIYO) was essentially similar to that seen in the cytochrome c assay. Inhibition of endogenous Cu/Zn SOD with diethyldithiocarbamate (DETCA, 3 m M , 120 min) in BRP muscle strips, followed by addition of the superoxide anion generator, LY 83583 (1 μ M ), resulted in almost complete abolition of nitrergic relaxation (4 Hz, 10 s). Authentic Cu/Zn SOD (1–300 u ml −1 ), CuSO 4 (0.1–300 μ M ), MnCl 2 (0.1–100 μ M ) and MnTMPyP (10–300 μ M ) each restored nitrergic transmission by around 50%. However, CuDIPS (0.1–30 μ M ), MnTBAP (0.1–100 μ M ), tempol (10 μ M –3 m M ), PTIYO (1–300 μ M ) and tiron (10 μ M –10 m M ) all failed to restore nitrergic transmission. The ability of MnTMPyP to restore nitrergic neurotransmission may therefore provide a lead in the development of SOD mimetics as therapeutic agents in the treatment of neuropathies associated with oxidant stress.