Effect of potassium channel blockade and alpha 2-adrenoceptor activation on the release of nitric oxide from non-adrenergic non-cholinergic nerves.
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 microM) and tetraethylammonium (TEA, 1 mM) and the more selective blocker of Ca(2+)-activated K+ channels, charybdotoxin (Leiurus quinquestriatus venom (LQV), 0.4 microgram 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 microM), and by L-NG-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 microM) 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 microM). Neither UK-14,304 nor yohimbine affected the relaxations induced by exogenous NO (5 pmol) or GTN (10 pmol) on the aortic detector ring.3+
De Man
J G
JG
Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Belgium.
Boeckxstaens
G E
GE
Herman
A G
AG
Pelckmans
P A
PA
D015761:4-Aminopyridine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D000068438:Brimonidine Tartrate; D018999:Charybdotoxin; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D012604:Scorpion Venoms / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D015221:Potassium Channels; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D019335:Nitroarginine; D015016:Yohimbine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D000068438:Brimonidine Tartrate; D001120:Arginine; D015761:4-Aminopyridine