Alpha 2-adrenoceptor-mediated modulation of the nitrergic innervation of the canine isolated ileocolonic junction.
1. The effects of specific alpha-adrenoceptor agonists and antagonists on electrically-evoked non-adrenergic non-cholinergic (NANC) relaxations, previously demonstrated as nitrergic, were investigated in isolated circular muscle strips of the canine ileocolonic junction. 2. During a substance P-induced contraction and in the presence of atropine and guanethidine, the specific alpha 1-adrenoceptor agonist, phenylephrine and antagonist, prazosin, as well as the specific alpha 2-adrenoceptor antagonist, yohimbine, had no effect on the NANC relaxations evoked by electrical field stimulation. In contrast, clonidine and the more specific alpha 2-adrenoceptor agonist, UK-14,304, significantly reduced the electrically-induced relaxations, preferentially those in response to low frequency stimulation. The inhibitory effect of UK-14,304 on these relaxations was antagonized by yohimbine. 3. During a noradrenaline-induced contraction, clonidine, but not UK-14,304 significantly augmented the relaxations to electrical stimulation. 4. The adrenoceptor agonists and antagonists used had no effect on concentration-response curves to NO or on the relaxation induced by nitroglycerin. 5. These results indicate that stimulation of prejunctional alpha 2-adrenoceptors inhibits the nitrergic NANC relaxations induced by field stimulation and thus suggest prejunctional regulation of nitric oxide release via alpha 2-adrenoceptors in the canine ileocolonic junction.
Boeckxstaens
G E
GE
Division of Gastroenterology, Faculty of Medicine, University of Antwerp, Antwerpen-Wilrijk, Belgium.
De Man
J G
JG
Pelckmans
P A
PA
Herman
A G
AG
Van Maercke
Y M
YM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D002415:Cats; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D009569:Nitric Oxide; D013373:Substance P; D001285:Atropine; D005996:Nitroglycerin; D009638:Norepinephrine; D006145:Guanethidine