Prejunctional modulation of the nitrergic innervation of the canine ileocolonic junction via potassium channels.
1. The effects of different K+ channel blockers were studied on nitric oxide (NO)-mediated non-adrenergic non-cholinergic (NANC) relaxations in the canine ileocolonic junction. 2. The non-selective blockers of K+ channels, 4-aminopyridine (4-AP) and tetraethylammonium (TEA) and the blocker of large conductance Ca(2+)-activated K+ channels, charybdotoxin, potently enhanced the NANC relaxations induced by low frequency stimulation. The blocker of small conductance Ca(2+)-activated K+ channels, apamin, had no effect on electrically-induced NANC relaxations. 3. NANC nerve-mediated relaxations induced by adenosine 5'-triphosphate (ATP), acetylcholine (ACh) and gamma-aminobutyric acid (GABA) were significantly enhanced by 4-AP and charybdotoxin but not by apamin. TEA significantly enhanced the NANC relaxations in response to GABA and ATP while that in response to ACh was abolished. 4. None of the K+ channel blockers had an effect on the dose-response curve to NO, on the noradrenaline-induced contraction or on the relaxation to nitroglycerine (GTN). 5. From these results we conclude that inhibition of prejunctional K+ channels increases the nitrergic relaxations induced by electrical and chemical receptor stimulation of NANC nerves and thus suggests a regulatory role for these prejunctional K+ channels in the release of NO from NANC nerves in the canine ileocolonic junction.
De Man
J G
JG
Division of Gastroenterology, Faculty of Medicine, University of Antwerp (UIA), Wilrijk, Belgium.
Boeckxstaens
G E
GE
Pelckmans
P P
PP
De Winter
B Y
BY
Herman
A G
AG
Van Maercke
Y M
YM
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D003106:Colon / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D007082:Ileum / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D015221:Potassium Channels; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D005996:Nitroglycerin; D000109:Acetylcholine; D009638:Norepinephrine