Characterization of myenteric neuropathy in the jejunum of spontaneously diabetic BB-rats.
Decreased gastric expression and function of neuronal nitric oxide synthase (nNOS) has been proposed as a potential mechanism underlying diabetic gastroparesis. As gastric nNOS expression is vagally controlled, these changes might occur secondarily to vagal neuropathy. In addition, it is unclear whether other inhibitory neurotransmitters are also involved. We used the type 1 diabetic BioBreeding (BB)-rat model to study jejunal motor control and nNOS expression, which is independent of the vagus. Jejunal segments were used for in vitro contractility studies, and measurement of nNOS expression after 8 or 16 weeks of diabetes compared with age- and sex-matched controls. Unlike electrical field stimulation and acetylcholine (ACh)-induced contractions, non-adrenergic non-cholinergic (NANC) relaxations were significantly reduced in diabetic rats. In contrast to control rats, NANC relaxations in diabetic rats were N(omega)-nitro-L-arginine methyl ester (L-NAME) insensitive. Jejunal nNOS expression was significantly decreased in diabetic rats. Both in diabetic and in control animals, L-NAME resistant relaxations were sensitive to P(2)-receptor antagonists. In the jejunum of spontaneously diabetic rats, decreased nitric oxide responsiveness and decreased nNOS protein expression occur while purinergic transmission is unaffected. These findings indicate that nitrergic enteric neuropathy may be a primary dysfunction in diabetes, independent from vagal dysfunction.
Zandecki
M
M
Center for Gastroenterological Research, Catholic University Leuven, Leuven, Belgium.
Vanden Berghe
P
P
Depoortere
I
I
Geboes
K
K
Peeters
T
T
Janssens
J
J
Tack
J
J
D000818:Animals; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D005767:Gastrointestinal Diseases / Q000473:pathology / Q000503:physiopathology; D007583:Jejunum / Q000033:anatomy & histology / Q000294:innervation*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009126:Muscle Relaxation / Q000502:physiology; D009197:Myenteric Plexus / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
D004791:Enzyme Inhibitors; D052248:Nitric Oxide Synthase Type I; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D019331:NG-Nitroarginine Methyl Ester