Abstract：
BACKGROUND AND PURPOSE:Nitric oxide (NO) is known to activate NO-sensitive guanylyl cyclase (NO-GC) and to elicit cGMP production. However, NO has also been proposed to induce cGMP-independent effects. It is accepted practice to use specific NO-GC inhibitors, such as ODQ or NS2028, to assess cGMP-dependent NO effects. Consequently, NO-induced reactions seen in the presence of these inhibitors commonly serve as an affirmation of cGMP independence. EXPERIMENTAL APPROACH:We evaluated the use of ODQ to discriminate between cGMP-dependent and cGMP-independent NO effects. NO-GC-expressing HEK cells, platelets and tissues from wild type (WT) and NO-GC-deficient mice (GCKO) were used. KEY RESULTS:NO donors led to accumulation of cGMP in platelets and GC-expressing HEK cells and induced phosphorylation of the vasodilator-stimulated phosphoprotein in platelets; both effects were reduced by ODQ. High concentrations of NO donors, however, overrode the inhibitory effect of ODQ. Correspondingly, ODQ inhibited but did not fully eliminate NO-induced relaxation of aorta and fundus from WT mice. Relaxation induced by endogenously released NO was fully or partially inhibited by ODQ in fundus and aorta, respectively. In aorta and fundus of GCKO mice NO-induced relaxation was absent and served as standard for complete NO-GC inhibition. CONCLUSIONS AND IMPLICATIONS:High NO concentrations can overcome the inhibitory effect of ODQ on NO-GC. Smooth muscle relaxation induced by NO donors/endogenously released NO in the presence of ODQ in WT was absent in GCKO animals indicating involvement of NO-GC. Accordingly, NO-induced effects in the presence of ODQ do not necessarily prove cGMP independence.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Lies B,Groneberg D,Gambaryan S,Friebe Adoi
10.1111/bph.12275subject
Has Abstractpub_date
2013-09-01 00:00:00pages
317-27issue
2eissn
0007-1188issn
1476-5381journal_volume
170pub_type
杂志文章abstract：:1. The vascular actions of the proteinase-activated receptor-2-activating peptides (PAR2APs), SLIGRL-NH2 (SL-NH2) and SLIGKV-NH2 (KV-NH2) as well as the reverse-sequence peptide, LSIGRL-NH2 (LS-NH2) and an N-acylated PAR2AP derivative, trans-cinnamoyl-LIGRLO-NH2 (tcLI-NH2), were studied in rat intact and endothelium-d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701726
更新日期：1998-04-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：
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abstract：:1. The cyclic nucleotide phosphodiesterase (PDE) of guinea-pig eosinophils was partially characterized and the effects of selective inhibitors of PDE isoenzymes upon opsonized zymosan (OZ)-stimulated respiratory burst were studied. 2. PDE activity in eosinophil lysates appeared to be membrane-associated, displayed sub...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1991.tb09790.x
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb16475.x
更新日期：1984-08-01 00:00:00
abstract：:1. The effects of palytoxin (PTX) isolated from Palythoa tubercurosa were tested on the isolated intra-arterially perfused spinal cord of the frog. The resting and evoked potentials were recorded by means of a sucrose-gap technique. 2. PTX caused a marked depolarization of both ventral and dorsal roots. The minimum ef...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1980.tb10975.x
更新日期：1980-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Mitochondrial aldehyde dehydrogenase (ALDH-2) has been shown to provide a pathway for bioactivation of organic nitrates and to be prone to desensitization in response to highly potent, but not to less potent, nitrates. We therefore sought to support the hypothesis that bioactivation by ALDH-2 cri...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707116
更新日期：2007-02-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11530.x
更新日期：1988-06-01 00:00:00
abstract：:1. The effect of the novel ET(A) receptor antagonist LBL 031 and other selective and mixed endothelin receptor antagonists on endothelin-1 (ET-1)-induced and lipopolysaccharide (LPS)-induced microvascular leakage was assessed in rat airways. 2. Intravenously administered ET-1 (1 nmole kg(-1)) or LPS (30 mg kg(-1)) cau...
journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0703691
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journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703356
更新日期：2000-06-01 00:00:00
abstract：:1. The effect of in vivo desensitization to leukotriene B4 (LTB4) on eosinophil infiltration in response to recombinant C5a was examined in guinea-pig skin. 2. LTB4 (10-300 ng) and C5a (1-10 micrograms) caused a dose-dependent increase in the levels of eosinophil peroxidase activity (a measure of eosinophil infiltrati...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb16182.x
更新日期：1994-09-01 00:00:00
abstract：:1. The aim of the present study was to test the effects of DAU 6215 (endo-N-(8-methyl-8-azabicyclo-[3.2.1]-octo-3-yl)-2,3-dihydro-2-ox o-1H- benzimidazole-1-carboxamide carboxamide hydrochloride), a newly synthesized, selective 5-hydroxytryptamine3 (5-HT3) antagonist, on the cell membrane properties and on characteriz...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13132.x
更新日期：1994-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707284
更新日期：2007-07-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb09644.x
更新日期：1974-06-01 00:00:00
abstract：:1. The effects of intradermally injected prostaglandins (PGs) E(1), E(2), F(1alpha) and F(2alpha) have been examined in the rat and in man.2. PGE(1) and PGE(2) caused an increase in local vascular permeability in rat skin; their potency was comparable with that of other putative mediators of inflammation (histamine, b...
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb09934.x
更新日期：1971-01-01 00:00:00
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doi：10.1038/sj.bjp.0703583
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doi：10.1111/j.1476-5381.1992.tb14482.x
更新日期：1992-09-01 00:00:00
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journal_title：British journal of pharmacology
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更新日期：2011-05-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0701710
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pub_type： 杂志文章
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更新日期：2004-10-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0702924
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journal_title：British journal of pharmacology
pub_type： 杂志文章
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb14635.x
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701373
更新日期：1997-09-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb12919.x
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abstract：:1. The alpha 2-adrenoceptor binding sites of rabbit spleen and rat kidney, labelled with [3H]-rauwolscine, were characterized using a range of subtype selective ligands. 2. In rabbit spleen, the alpha-2-adrenoceptor binding sites displayed high affinity for oxymetazoline and WB 4101 and low affinity for prazosin and c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12968.x
更新日期：1990-03-01 00:00:00
