Membrane trapping of carbon-11-labeled 1,2-diacylglycerols as a basic concept for assessing phosphatidylinositol turnover in neurotransmission process.
The uptake mechanism of 1,2-[11C]diacylglycerols (DAG) was studied and its use as a probe for the measurement of phosphatidylinositol (PI) turnover was verified. A method of synthesis for producing rac-1,2-[11C]DAG using [11C]ethylketene was developed to label the 1- or 3-hydroxyl group of 2-monoacylglycerol. After intravenous injection, these tracers were metabolized rapidly in the rat brain cortex to phosphatidic acids, phosphatidylinositols and phosphatidylinositol phosphates. The brain cortex anesthetized by barbiturate, which represents inhibited state of synaptic transmission, did not produce differences in uptake values between sn-1,2-[11C]DAG and rac-1,2-[11C]DAG. However, in the liver, lung, and pancreas under the same conditions, the uptake values of rac-1,2-[11C]DAG were higher than those of sn-1,2-[11C] DAG, in which the labeling position was on the 2-hydroxyl group in the sn type. These findings suggest that the lipase activity in the brain should be disregarded because lipase predominantly hydrolyzes the 1- or 3-position of rac-1,2-[11C] DAG, which should be the main factor producing the differences in uptake values in other organs. Cholinergic stimulation prompted accumulation of 1,2-[11C]DAG in the conscious rat brain. In conclusion, sn-1,2-[11C]DAG, administered even in the racemic mixture, could serve as a tracer that becomes mixed with receptor-linked PI turnover and could accumulate in the brain based on the membrane trapping mechanism.
Imahori
Y
Y
Department of Neurosurgery, Kyoto Prefectural University of Medicine, Japan.
Fujii
R
R
Ueda
S
S
Matsumoto
K
K
Wakita
K
K
Ido
T
T
Nariai
T
T
Nakahashi
H
H
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D004075:Diglycerides / Q000138:chemical synthesis / Q000737:chemistry; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D004075:Diglycerides; D010716:Phosphatidylinositols; D002245:Carbon Dioxide