NO releases bombesin-like immunoreactivity from enteric synaptosomes by cross-activation of protein kinase A
Kurjak, M.; Fritsch, R.; Saur, D.; Schusdziarra, V.; Allescher, H.D.
American Journal of Physiology 276(6): G1521-G1530
1999
ISSN/ISBN: 0002-9513 PMID: 10362657 Document Number: 509520
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; 10-7 to 10-4 M) significantly stimulated BLI release. In the presence of the NO scavenger oxyhemoglobin (10-3 M) or the guanylate cyclase inhibitor ODQ (10-5 M), SNAP-induced BLI release was antagonized. In addition, SNAP increased the synaptosomal cGMP content and elevation of cGMP levels by zaprinast (3 10-5 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 (10-8 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. Reprinted by permission of the publisher.