Involvement of the somatostatin-2 receptor in the anti-convulsant effect of angiotensin IV against pilocarpine-induced limbic seizures in rats
Version of Record online: 12 JUN 2006
Journal of Neurochemistry
Volume 98, Issue 4, pages 1100–1113, August 2006
How to Cite
Stragier, B., Clinckers, R., Meurs, A., De Bundel, D., Sarre, S., Ebinger, G., Michotte, Y. and Smolders, I. (2006), Involvement of the somatostatin-2 receptor in the anti-convulsant effect of angiotensin IV against pilocarpine-induced limbic seizures in rats. Journal of Neurochemistry, 98: 1100–1113. doi: 10.1111/j.1471-4159.2006.03942.x
- Issue online: 19 JUN 2006
- Version of Record online: 12 JUN 2006
- Received December 13, 2005; revised manuscript received March 28, 2006; accepted March 28, 2006.
- angiotensin IV;
- insulin-regulated aminopeptidase;
The anti-convulsant properties of angiotensin IV (Ang IV), an inhibitor of insulin-regulated aminopeptidase (IRAP) and somatostatin-14, a substrate of IRAP, were evaluated in the acute pilocarpine rat seizure model. Simultaneously, the neurochemical changes in the hippocampus were monitored using in vivo microdialysis. Intracerebroventricularly (i.c.v.) administered Ang IV or somatostatin-14 caused a significant increase in the hippocampal extracellular dopamine and serotonin levels and protected rats against pilocarpine-induced seizures. These effects of Ang IV were both blocked by concomitant i.c.v. administration of the somatostatin receptor-2 antagonist cyanamid 154806. These results reveal a possible role for dopamine and serotonin in the anti-convulsant effect of Ang IV and somatostatin-14. Our study suggests that the ability of Ang IV to inhibit pilocarpine-induced convulsions is dependent on somatostatin receptor-2 activation, and is possibly mediated via the inhibition of IRAP resulting in an elevated concentration of somatostatin-14 in the brain.