CSF Guanosine Levels Following Intraperitoneal Guanosine or GMP

This article is interesting and shows that the baseline CSF guanosine, GMP, and adenosine levels are, in each case, less than 500 nM. Following 7.5 mg/kg of either intraperitoneal guanosine or GMP, at 30 minutes post-administration, the authors found that the CSF guanosine level had increased to two or three times the baseline value. The CSF GMP and adenosine levels did not increase significantly in response to i.p. guanosine or GMP. The peak CSF guanosine concentration occurred in response to 7.5 mg/kg i.p. GMP and was in excess of 3 uM, and the increases in CSF guanosine were dose-dependent:

http://www.ncbi.nlm.nih.gov/pubmed/15044076 (Soares et al., 2004)

It's strange that the researchers are able to show neuroprotective effects in response to elevations in CSF guanosine that are so small, at least in comparison to the concentrations used in in vitro research in cultured astrocytes. Purines are known to be metabolized and transported into cells extremely rapidly, and, in spite of such low CSF guanosine concentrations, there may be significant elevations in intracellular guanosine in astrocytes or neurons. I remember reading that, despite the grave problems with S-adenosylmethionine bioavailability, at least one of the studies using i.m. S-adenosylmethionine to treat arthritis showed very minimal elevations in plasma S-adenosylmethionine that had nonetheless been accompanied by clinical improvements.