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Nitric oxide regulates the release of somatostatin from cultured gastric rabbit primary D-cells

journal contribution
posted on 2023-05-17, 08:06 authored by Arebi, N, Healey, ZV, Bliss, PW, Ghatei, M, Van Noorden, S, Playford, RJ, Calam, J
Background & Aims: Neuronal nitric oxide synthase (nNOS) is present in gastric D-cells. Mucosal somatostatin is diminished in H. pylori gastritis, where production of nitric oxide (NO) is increased. Therefore, we investigated the role of NO in D-cell function and the effects of prolonged exposure of D-cells to NO. Methods: Rabbit gastric D-cells were cultured. Somatostatin-14 was measured after 2 hours to examine the effects of arginine, nitric oxide sythase (NOS) inhibitors, and NO donors. Some cells were preincubated with a slow releasing NO donor for 12 hours. Results are expressed as percentage of total cell content. Nitrate content was measured by chemiluminescent assay. Results: L-arginine increased somatostatin-14 release in the presence of CCK8 from 4.4% ± 0.5% to 6.4% ± 0.4% (P < 0.02), and this was accompanied by NO release from 27 ± 7 μmol/L to 86 ± 12 μmol/L (P = 0.001). D-arginine and L-lysine had no effect. NOS inhibitors LNNA, SMT, and 7Nl significantly attenuated the stimulatory response to L-arginine. NO donors sodium nitroprusside (SNP), 1 mmol/L, and S-nitroso-N-acetyl-D-L-penicillamine, 0.1 mmol/L, significantly increased basal and cholecystokinin-8 (CCK8) stimulated somatostatin release. Oxyhemoglobin attenuated the effect of SNP but not of L-arginine. Neither cyclic guanosine monophosphate nor guanylate cyclase were involved in the response to NO. However, inhibition of adenosine diphosphate (ADP) ribosyltransferase significantly decreased the response to L-arginine. Preincubation for 12 hours with 150 μmol/L (Z)-1-[(2- aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate; IP3, inositol triphosphate decreased the 2-hour cellular response to CCK8 and SNP. Conclusions: NO regulates rabbit D-cells. Acute exposure stimulates somatostatin mediated by ADP ribosylation, whereas long-term exposure reduces cellular responses to stimuli. The latter pathway may be responsible for the suppression of somatostatin in H. pylori gastritis.

History

Publication title

Gastroenterology: A Journal Devoted to The Clinical and Basic Studies of The Digestive Tract and Liver

Volume

123

Pagination

566-576

ISSN

0016-5085

Department/School

College Office - College of Health and Medicine

Publisher

W B Saunders Co

Place of publication

Independence Square West Curtis Center, Ste 300, Philadelphia, USA, Pa, 19106-3399

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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    University Of Tasmania

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