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Title
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Effect of potassium channel blockade and -adrenoceptor activation on the release of nitric oxide from non-adrenergic noncholinergic nerves
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Author
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Abstract
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| 1 Using a superfusion bioassay cascade, we studied the effect of K+ channel blockers and alpha(2)-adrenoceptor agents on the release of a transferable factor, previously characterized as nitric oxide (NO) or a nitric oxide-related substance (NO-R), in response to non-adrenergic non-cholinergic (NANC) nerve stimulation in the canine ileocolonic junction (ICJ). 2 The non-selective K+ channel blockers, 4-aminopyridine (4-AP, 50 mu M) and tetraethylammonium (TEA, 1 mM) and the more selective blocker of Ca2+-activated K+ channels, charybdotoxin (Leiurus guinquestriatus venom (LQV), 0.4 mu g ml(-1)), significantly enhanced the release of NO-R induced by low frequency stimulation (2-4 Hz). In the presence of 4-AP and TEA, the release of NO-R was nearly abolished by tetrodotoxin (2 mu M), and by L-N-G-nitroarginine (L-NOARG, 0.1 mM). Relaxations induced by direct injection of exogenous NO (5-50 pmol) or nitroglycerin (GTN, 10-30 pmol) onto the rabbit aortic detector ring were not affected. 3 The alpha(2)-adrenoceptor agonist, UK-14,304 (0.3 mu M) inhibited the release of NO-R induced by low (2-4 Hz), but not that induced by high (16 Hz), frequency stimulation. This inhibitory effect was completely reversed by the alpha(2)-adrenoceptor antagonist, yohimbine (0.3 mu M). Neither UK-14,304 nor yohimbine affected the relaxations induced by exogenous NO (5 pmol) or GTN (10 pmol) on the aortic detector ring. 4 On the other hand, in the presence of the K+ channel blockers 4-AP (50 mu M) or charybdotoxin (LQV, 0.4 mu g ml(-1)), UK-14,304 (0.3 mu M) failed to inhibit the electrically-induced release of NO-R. 5 From these results, we conclude that the electrically-induced release of NO-R from NANC nerves of the canine ICJ is enhanced by K+ channel blockers but inhibited by alpha(2)-adrenoceptor activation. In addition, these results suggest that the prejunctional modulation of NO-R release by alpha(2)-adrenoceptors may involve neuronal K+ channels. |
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Language
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English
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Source (journal)
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British journal of pharmacology. - London
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Publication
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London
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1994
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ISSN
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0007-1188
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Volume/pages
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112
:1
(1994)
, p. 341-345
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ISI
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A1994NH08400056
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Full text (publisher's version - intranet only)
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