Induction of neuronal nitric oxide synthase by sympathetic denervation is mediated via alpha 2-adrenoceptors in the jejunal myenteric plexus.
Nitric oxide (NO) is an important nonadrenergic, non-cholinergic (NANC) inhibitory neurotransmitter in the gastrointestinal tract. In previous studies, neuronal nitric oxide synthase (nNOS) in the jejunal myenteric plexus, a key enzyme responsible for the release of NO, has been demonstrated to increase after splanchinic ganglionectomy (sympathetic nerve transection). The alpha2-adrenoceptor is known to be one of the most important receptors which controls intestinal motility. In the present study, we examined the effect of application of the alpha2-adrenoceptor agonist, clonidine hydrochloride, on nNOS expression in the rat jejunal myenteric plexus after splanchinic ganglionectomy. Clonidine (0.1-1 mg/kg, i.p.) or saline was administered for 5 days after the splanchinic ganglionectomy. The nNOS expression and nNOS mRNA were detected by immunohistochemistry and in situ hybridization for nNOS mRNA, respectively. In the rats treated with vehicle after the splanchinic ganglionectomy, nNOS expression in the myenteric plexus significantly increased compared with sham-operated rats. The increases in nNOS protein and mRNA after splanchinic ganglionectomy were significantly reversed by clonidine treatment. Clonidine-treated naive rats showed no difference in nNOS expression compared with sham-operated rats. These data suggest that nNOS expression in the jejunal myenteric plexus after splanchinic ganglionectomy is regulated by the alpha2-adrenoceptor and that the alpha2-adrenoceptor may play an important role in abnormal intestinal motility following splanchinic ganglionectomy in rat jejunum.
Nishizaki
Kazushi
K
Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Hyogo Nishinomiya 663-8501, Japan.
Nakao
Koji
K
Ishii
Hiromitsu
H
Yamanaka
Hiroki
H
Tokunaga
Atsushi
A
Nakagawa
Kazuhiko
K
Yamamura
Takehira
T
Noguchi
Koichi
K
D000818:Animals; D003714:Denervation / Q000379:methods; D004790:Enzyme Induction / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000737:chemistry / Q000201:enzymology*; D007583:Jejunum / Q000737:chemistry / Q000201:enzymology* / Q000294:innervation*; D008297:Male; D009197:Myenteric Plexus / Q000737:chemistry / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000032:analysis / Q000378:metabolism*
D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat