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| Content Provider | PubMed Central |
|---|---|
| Author | Harrison, S. Spina, D. Page, C. P. |
| Copyright Year | 1997 |
| Abstract | 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. 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 μM), the non-selective β-adrenoceptor antagonist, propranolol (1 μM), the neutral endopeptidase inhibitor thiorphan (10 μM) and the cyclo-oxygenase inhibitor, indomethacin (5 μM). Okadaic acid significantly attenuated eNANC contractile responses (% inhibition) elicited by EFS (0.01 μM, 15.2±26.9%; 0.03 μM, 30.4±13.9%; 0.01 μM, 39.8±5.1%; 0.3 μM, 59.5±8.7%; 1 μM 77.8±7.8%; P<0.05, n=4). In contrast, the inactive analogue 1-Nor okadaone (0.3 μM) 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). 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, Nω-nitro-L-arginine methyl ester (L-NAME, 30 μM). 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). Okadaic acid (0.3 μM) 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). Okadaic acid (0.01–1 μM) did not appear to reverse substance P-induced tone. The maximal relaxant response (% reversal of substance P-induced tone) mediated by okadaic acid (1 μM) 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 μM) failed to augment isoprenaline-induced relaxation repsonses in substance P contracted bronchus (okadaic acid, 6.5±0.4 vs DMSO, 5.9±0.3; P>0.05, n=9). These results indicate that protein phosphatases appear to regulate the release of sensory neuropeptides from airway sensory nerves in response to electrical field stimulation. |
| Related Links | http://dx.doi.org/10.1038/sj.bjp.0701114 |
| Starting Page | 181 |
| File Format | |
| ISSN | 00071188 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 121 |
| Language | English |
| Publisher Date | 1997-05-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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