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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wu, C. C. Hwang, T. L. Teng, C. M. |
| Description | Author Affiliation: Hwang TL ( Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.) |
| Abstract | To clarify further the role of cyclic GMP in mediating the relaxant response in guinea-pig trachea induced by sodium nitroprusside (SNP), the effects of soluble guanylyl cyclase inhibitors, methylene blue and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) on SNP-induced muscle relaxation and cyclic GMP accumulation were determined. SNP (0.3-100 microM) evoked a concentration-dependent relaxation of guinea-pig isolated tracheas precontracted with 0.3 microM carbachol. Preincubation of the preparations with methylene blue (10, 30 and 100 microM) resulted in a slight but concentration-dependent prevention of the relaxant response to SNP. In contrast, the relaxation to SNP was extensively prevented by 3 microM ODQ and almost abolished by 10 microM ODQ. SNP (30 microM) induced a significant elevation of cyclic GMP accumulation (from 1.34+/-0.14 to 5.39+/-0.28 pmol mg(-1) protein, n= 5; P<0.001), which was partially attenuated by 100 microM methylene blue (3.11+/-0.51 pmol mg(-1) protein, n=5; P<0.05), whereas completely abolished by 10 microM ODQ (1.31+/-0.28 pmol mg(-1) protein, n = 5; P<0.001). Methylene blue, but not ODQ and Nomega-nitro-L-arginine methyl ester (L-NAME), caused a concentration-dependent contraction in the tracheal preparation. The tension produced by 100 microM methylene blue was 41.8+/-4.3% (0.3 microM carbachol as 100%; n = 12). Moreover, the non-selective muscarinic receptor antagonist atropine and the M3-selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodine greatly inhibited the contractile effect evoked by methylene blue (100 microM). In conclusion, this study provides substantial evidence that SNP-induced muscle relaxation in guinea-pig trachea is completely via a cyclic GMP-dependent mechanism. Furthermore, ODQ, but not methylene blue, will likely become an important tool in differentiating between cyclic GMP-dependent and -independent effects of nitric oxide. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 125 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1998-11-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Enzyme Inhibitors Pharmacology Guanylate Cyclase Antagonists & Inhibitors Methylene Blue Muscle Relaxation Drug Effects Nitroprusside Oxadiazoles Quinoxalines Trachea Physiology Vasodilator Agents Animals Cyclic GMP Metabolism Drug Interactions Guinea Pigs Mice Muscle, Smooth NG-Nitroarginine Methyl Ester Nitric Oxide Signal Transduction Solubility Comparative Study Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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