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Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats.
Gastroenterology 1997; 113(5):1535-44G

Abstract

BACKGROUND & AIMS

The mechanism responsible for defective gastric accommodation in diabetes is unknown. The aim of this study was to investigate if this abnormality is due to a defective nitric oxide pathway secondary to impaired nitric oxide synthase (NOS) expression in the gastric myenteric plexus.

METHODS

To test this hypothesis, we studied nonadrenergic, noncholinergic (NANC) relaxation, NOS activity, NADPH diaphorase histochemistry, NOS immunohistochemistry, NOS immunoblotting, and NOS messenger RNA expression in the gastric myenteric plexus of spontaneously diabetic biobreeding/Worcester (BB/W) rats. Age-matched nondiabetic Wistar rats were used as controls.

RESULTS

Gastric neuromuscular preparations from control rats showed a frequency-dependent NANC relaxation in response to transmural stimulation. This relaxation was markedly antagonized by N(G)-nitro-L-arginine-methyl ester, indicating mediation by the neuronal release of NO. The NANC relaxation in gastric muscle preparations obtained from diabetic BB/W rats was significantly impaired. The number of NOS-immunoreactive cells in the gastric myenteric plexus and the NOS activity were significantly reduced in diabetic BB/W rats, suggesting that NOS synthesis is impaired in diabetes. Northern blot analysis showed that the density of NOS messenger RNA bands at 9.5 kilobases was significantly reduced in the gastric tissues of diabetic BB/W rats.

CONCLUSIONS

These results indicate that gastric relaxation in diabetics is hampered mainly by impaired NOS expression in the gastric myenteric plexus.

Authors+Show Affiliations

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0362, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9352855

Citation

Takahashi, T, et al. "Impaired Expression of Nitric Oxide Synthase in the Gastric Myenteric Plexus of Spontaneously Diabetic Rats." Gastroenterology, vol. 113, no. 5, 1997, pp. 1535-44.
Takahashi T, Nakamura K, Itoh H, et al. Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats. Gastroenterology. 1997;113(5):1535-44.
Takahashi, T., Nakamura, K., Itoh, H., Sima, A. A., & Owyang, C. (1997). Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats. Gastroenterology, 113(5), pp. 1535-44.
Takahashi T, et al. Impaired Expression of Nitric Oxide Synthase in the Gastric Myenteric Plexus of Spontaneously Diabetic Rats. Gastroenterology. 1997;113(5):1535-44. PubMed PMID: 9352855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impaired expression of nitric oxide synthase in the gastric myenteric plexus of spontaneously diabetic rats. AU - Takahashi,T, AU - Nakamura,K, AU - Itoh,H, AU - Sima,A A, AU - Owyang,C, PY - 1997/11/14/pubmed PY - 1997/11/14/medline PY - 1997/11/14/entrez SP - 1535 EP - 44 JF - Gastroenterology JO - Gastroenterology VL - 113 IS - 5 N2 - BACKGROUND & AIMS: The mechanism responsible for defective gastric accommodation in diabetes is unknown. The aim of this study was to investigate if this abnormality is due to a defective nitric oxide pathway secondary to impaired nitric oxide synthase (NOS) expression in the gastric myenteric plexus. METHODS: To test this hypothesis, we studied nonadrenergic, noncholinergic (NANC) relaxation, NOS activity, NADPH diaphorase histochemistry, NOS immunohistochemistry, NOS immunoblotting, and NOS messenger RNA expression in the gastric myenteric plexus of spontaneously diabetic biobreeding/Worcester (BB/W) rats. Age-matched nondiabetic Wistar rats were used as controls. RESULTS: Gastric neuromuscular preparations from control rats showed a frequency-dependent NANC relaxation in response to transmural stimulation. This relaxation was markedly antagonized by N(G)-nitro-L-arginine-methyl ester, indicating mediation by the neuronal release of NO. The NANC relaxation in gastric muscle preparations obtained from diabetic BB/W rats was significantly impaired. The number of NOS-immunoreactive cells in the gastric myenteric plexus and the NOS activity were significantly reduced in diabetic BB/W rats, suggesting that NOS synthesis is impaired in diabetes. Northern blot analysis showed that the density of NOS messenger RNA bands at 9.5 kilobases was significantly reduced in the gastric tissues of diabetic BB/W rats. CONCLUSIONS: These results indicate that gastric relaxation in diabetics is hampered mainly by impaired NOS expression in the gastric myenteric plexus. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/9352855/Impaired_expression_of_nitric_oxide_synthase_in_the_gastric_myenteric_plexus_of_spontaneously_diabetic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016508597005192 DB - PRIME DP - Unbound Medicine ER -