Choline incorporation into phospholipids in brain areas from spontaneously hypertensive rats: effect of oxiracetam treatment.
It has been demonstrated that spontaneously hypertensive rats (SHR) develop severe hypertension and cerebrovascular lesions on drinking 1% NaCl from weaning. These animals present a learning and memory impairment as well as impairment of both energy metabolism and membrane phospholipid turnover. We tested both choline uptake into the cells and incorporation into choline phosphoglyceride (CPG) by incubating slices from hippocampus and cortex. After 5 min of incubation, a noticeable decrease in free labelled choline content inside the cells as well as its incorporation into phospho-choline (PC) and CPG were found in the brain of SHR, as compared to Wistar-Kyoto (WK) rats. This may indicate that in the SHRs with cerebrovascular lesions there is a reduction in choline uptake which in turn causes a decline in CPG biosynthesis through de novo pathway. Oxiracetam treatment is able to restore the labeled choline content in the cells from SH rats, as well as the incorporation of choline into its derivatives PC and CPG, to the levels found in the WK or more. Tests performed in the presence of such a high affinity choline uptake as hemicholinium (HC) confirmed the capacity of oxiracetam to stimulate choline uptake into the cells even if the results obtained up to now are not sufficient to hypothesize a direct effect of oxiracetam on acetylcholine metabolism. In conclusion, from the results obtained it would seem reasonable to hypothesize that the effects of the drug above mentioned on the cholinergic system may be secondary to its effect on choline phosphoglycerides biosynthesis.
Nardella
C
C
Istituto di Biochimica e Chimica Medica, Università di Perugia.
Terracina
L
L
Brunetti
M
M
Avellini
L
L
De Medio
G E
GE
Gaiti
A
A
Belfiore
P
P
Mariani
O
O
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002794:Choline / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006426:Hemicholinium 3 / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010743:Phospholipids / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013574:Synaptosomes / Q000378:metabolism
D010713:Phosphatidylcholines; D010743:Phospholipids; D011619:Psychotropic Drugs; D011759:Pyrrolidines; D006426:Hemicholinium 3; D002794:Choline; C040619:oxiracetam