Document Detail


The effect of okadaic acid on non-adrenergic non-cholinergic contraction in guinea-pig isolated bronchus.
MedLine Citation:
PMID:  9154325     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. We have investigated the role of phosphatases in modulating contractile responses to electrical field stimulation (EFS), methacholine, substance P and capsaicin in guinea-pig isolated main bronchus by use of the phosphatase 1 and 2A inhibitor okadaic acid. 2. Non-adrenergic non-cholinergic (eNANC) contractile responses were elicited by EFS (3 Hz, 20 s, 0.5 ms max. voltage) in the guinea-pig isolated main bronchus in the presence of the non-selective muscarinic antagonist, atropine (1 microM), the non-selective beta-adrenoceptor antagonist; propranolol (1 microM), the neutral endopeptidase inhibitor thiorphan (10 microM) and the cyclo-oxygenase inhibitor, indomethacin (5 microM). Okadaic acid significantly attenuated eNANC contractile responses (% inhibition) elicited by EFS (0.01 microM, 15.2 +/- 26.9%; 0.03 microM, 30.4 +/- 13.9%; 0.01 microM, 39.8 +/- 5.1%; 0.3 microM, 59.5 +/- 8.7%; 1 microM 77.8 +/- 7.8%; P < 0.05, n = 4). In contrast, the inactive analogue 1-Nor okadaone (0.3 microM) failed to attenuate significantly eNANC contractile responses (% inhibition elicited by 1-Nor okadaone, -1.25 +/- 8.5% vs dimethylsulphoxide (DMSO), -13.5 +/- 21.5%; P > 0.05, n = 4). 3. Cholinergic contractile responses were elicited by EFS (1-30 Hz, 10 s, 0.5 ms max. voltage) in guinea-pig isolated bronchus in the presence of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 30 microM). Okadaic acid failed to attenuate significantly the contractile (% methacholine Emax) response elicited by EFS at all frequencies tested compared with the control (1 Hz, control, 22 +/- 7.9% vs okadaic acid, 18 +/- 7.7%; 3 Hz, control, 26 +/- 6.9% vs okadaic acid, 27 +/- 9.1%; 10 Hz, control, 36 +/- 7.6% vs okadaic acid, 33 +/- 8.9%; 30 Hz, control, 50 +/- 7.6% vs okadaic acid, 42 +/- 14%; P > 0.05, n = 4). 4. Okadaic acid (0.3 microM) failed to alter significantly the contractile potency (pD2) to capsaicin (okadaic acid, 9.0 +/- 0.5, vs DMSO, 9.2 +/- 0.4; P > 0.05 n = 6), substance P (okadaic acid, 7.6 +/- 0.3 vs DMSO, 8.2 +/- 0.2; P > 0.05 n = 7) or methacholine (okadaic acid, 6.4 +/- 0.2 vs DMSO, 6.4 +/- 0.3; P > 0.05 n = 4). 5. Okadaic acid (0.01-1 microM) did not appear to reverse substance P-induced tone. The maximal relaxant response (% reversal of substance P-induced tone) mediated by okadaic acid (1 microM) was 33 +/- 11.7% (n = 4), this was not significantly different from the DMSO (0.8%) or a time-dependent fall in tone of 34.3 +/- 23.1% (n = 4) and 33 +/- 15.8% (n = 4), respectively. Okadaic acid (0.3 microM) failed to augment isoprenaline-induced relaxation responses in substance P contracted bronchus (okadaic acid, 6.5 +/- 0.4 vs DMSO, 5.9 +/- 0.3; P > 0.05, n = 9). 6. These results indicate that protein phosphatases appear to regulate the release of sensory neuropeptides from airway sensory nerves in response to electrical field stimulation.
Authors:
S Harrison; D Spina; C P Page
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  121     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-07-16     Completed Date:  1997-07-16     Revised Date:  2008-11-20    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  181-6     Citation Subset:  IM    
Affiliation:
Sackler Institute of Pulmonary Pharmacology, Department of Respiratory Medicine, King's College School of Medicine & Dentistry, London.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bronchi / drug effects*
Dose-Response Relationship, Drug
Guinea Pigs
Male
Muscle Contraction / drug effects*
Okadaic Acid / pharmacology*
Chemical
Reg. No./Substance:
78111-17-8/Okadaic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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