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Effect of potassium channel blockade and α 2 ‐adrenoceptor activation on the release of nitric oxide from non‐adrenergic non‐cholinergic nerves
Author(s) -
Man Joris G.,
Boeckxstaens Guy E.,
Herman Arnold G.,
Pelckmans Paul A.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13074.x
Subject(s) - cholinergic , nitric oxide , adrenergic , potassium channel , blockade , potassium , chemistry , adrenergic beta antagonists , endocrinology , nitric oxide synthase , pharmacology , medicine , acetylcholine , propranolol , receptor , organic chemistry
1 Using a superfusion bioassay cascade, we studied the effect of K + channel blockers and α 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 μ m ) and tetraethylammonium (TEA, 1 m m ) and the more selective blocker of Ca 2+ ‐activated K + channels, charybdotoxin ( Leiurus quinquestriatus venom (LQV), 0.4 μg 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 μ m ), and by l ‐N G ‐nitroarginine ( l ‐NOARG, 0.1 m m ). 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 α 2 ‐adrenoceptor agonist, UK‐14,304 (0.3 μ 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 α 2 ‐adrenoceptor antagonist, yohimbine (0.3 μ 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 μ m ) or charybdotoxin (LQV, 0.4 μg ml −1 ), UK‐14,304 (0.3 μ 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 α 2 ‐adrenoceptor activation. In addition, these results suggest that the prejunctional modulation of NO‐R release by α 2 ‐adrenoceptors may involve neuronal K + channels.