The effect of nitric oxide (NO) on the release of bombesin-like immunoreactivity (BLI) was examined in synaptosomes of rat small intestine. The NO donor S-nitroso-N-acetylpenicillamine (SNAP; 10⁷ to 10⁴ M) significantly stimulated BLI release. In the presence of the NO scavenger oxyhemoglobin (10³ M) or the guanylate cyclase inhibitor ODQ (10⁵ M), SNAP-induced BLI release was antagonized. In addition, SNAP increased the synaptosomal cGMP content and elevation of cGMP levels by zaprinast (3 × 10⁵ M), an inhibitor of the cGMP-specific phosphodiesterase (PDE) type 5, and increased basal and SNAP-induced BLI release. NO-induced BLI release was blocked by Rp-adenosine 3',5'-cyclic monophosphorothioate (3 × 10⁵ M and 10⁴ M), an inhibitor of the cAMP-dependent protein kinase A, whereas KT-5823 (3 × 10⁶ M) and Rp-8-(4-chlorophenylthio)-cGMP (5 × 10⁵ M), inhibitors of the cGMP-dependent protein kinase G, had no effect. Because cGMP inhibits the cAMP-specific PDE3, thereby increasing cAMP levels, the role of PDE3 was investigated. Trequinsin (10⁸ M), a specific blocker of PDE3, stimulated basal BLI release but had no additive effect on NO-induced release, suggesting a similar mechanism of action. These data demonstrate that because of a cross-activation of cAMP-dependent protein kinase A by endogenous cGMP BLI can be released by NO from enteric synaptosomes.

nerve terminals; enteric nervous system; gastrin-releasing peptide; phosphodiesterase 3; phosphodiesterase 5; nitric oxide

This article has been cited by other articles:

				D. Saur, W. L. Neuhuber, B. Gengenbach, A. Huber, V. Schusdziarra, and H.-D. Allescher Site-specific gene expression of nNOS variants in distinct functional regions of rat gastrointestinal tract Am J Physiol Gastrointest Liver Physiol, February 1, 2002; 282(2): G349 - G358. [Abstract] [Full Text] [PDF]