AGI June 39/6

Kurjak, M., R. Fritsch, D. Saur, V. Schusdziarra, and H. D. Allescher. NO releases bombesin-like immunoreactivity from enteric synaptosomes by cross-activation of protein kinase A. Am. J. Physiol. 276 (Gastrointest. Liver Physiol. 39): G1521–G1530, 1999.—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; 1027 to 1024 M) significantly stimulated BLI release. In the presence of the NO scavenger oxyhemoglobin (1023 M) or the guanylate cyclase inhibitor ODQ (1025 M), SNAP-induced BLI release was antagonized. In addition, SNAP increased the synaptosomal cGMP content and elevation of cGMP levels by zaprinast (3 3 1025 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 38,58-cyclic monophosphorothioate (3 3 1025 M and 1024 M), an inhibitor of the cAMP-dependent protein kinase A, whereas KT-5823 (3 3 1026 M) and Rp-8-(4-chlorophenylthio)cGMP (5 3 1025 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 (1028 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.