| title: | L-arginine pathways and antidepressants |
|---|---|
| reg no: | ETF6081 |
| project type: | Estonian Science Foundation research grant |
| status: | accepted |
| institution: | University of Tartu |
| head of project: | Vallo Volke |
| duration: | 01.01.2005 - 31.12.2008 |
| description: | Nitric oxide is an unconventional neurotransmitter which has been implicated in several physiological and pathological processes. Interestingly, L-arginine is also metabolized by other enzymes besides NOS. Thus, arginine decarboxylase synthesizes agmatine, which is also a potential messenger molecule, and ornithine, which serves as a precursor of polyamine synthesis, is formed by arginase.Recent studies indicate that these pathways regulate each others activities by competing for L-arginine and also by other mechanisms. To study the activity of these pathways in a complex manner we have developed a simple and rapid HPLC method for simultaneous measurement of radiolabeled arginine, agmatine, citrulline and ornithine. Both preclinical and clinical evidence suggests a role of L-arginine pathways in depression. Thus administering of NOS inhibitor or agmatine induces antidepressant-like effect in forced swimming test. Few human studies have demonstrated increased plasma levels of nitrate in case of depression and bipolar disorder. The aim of the project is to study the role of L-arginine pathways in depression and to describe the effect of antidepressants on the activity of L-arginine pathways. Specific aims are as follows: 1. To further develop the HPLC based method: A. To include other biologically active molecules of these pathways - i.e., putrescine and other polyamines and to develop a method for measurement of agmatinase activity. B. To characterize optimal conditions for measuring the activities of different pathways in tissue homogenate, cell culture and organism levels (microdialysis). C. To apply the same principle in order to also measure the levels of unlabeled metabolites - by using electrochemical or some other type of detector. 2. To characterize the behavioural activity of different compounds affecting distinct L-arginine pathways in the forced swimming test. 3. To characterize the role of L-arginine pathways (especially the effect of agmatine) in regulating the 5-HT levels in the hippocampus and prefrontal cortex of freely moving rats and mice. 4. To characterize the effect of antidepressants on L-arginine pathways in cell culture and brain (microdialysis) after acute and chronic treatment. 5. To elucidate whether brain really synthesises agmatine. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Kertu Rünkorg | University of Tartu | research fellow | |
| 2. | Annika Volke | University of Tartu | research fellow | |
| 3. | Vallo Volke | University of Tartu | senior research fellow | |