Previous studies have shown that global
cerebral ischemia induced by
decapitation leads to the stimulated hydrolysis of poly-
phosphoinositides. In this study, the
decapitation model was used to further examine the temporal events related to metabolism of Ins(1,4,5)P3 and the release of
diacylglycerols (DGs) and
free fatty acids (FFAs) in the mouse brain. Since
lithium administration is known to inhibit
inositol monophosphatase activity in brain, the effects of acute
lithium injection on Ins(1,4,5)P3 metabolism were also examined.
Cerebral ischemia induced by
decapitation of C57 Bl/6J mice resulted in transient increases of Ins(1,4,5)P3, Ins(1,4)P2 and Ins(4)P which peaked at 35, 65 and 125 s, respectively. The level of Ins(1)P, however, was not altered. Mice administered
lithium by
intraperitoneal injection (8 meq/kg for 4 h) gave rise to a 40- and 4-fold increase in levels of Ins(1)P, Ins(4)P, respectively, a 20% increase in levels of Ins(1,4)P2 but no apparent changes in the levels of Ins(1,4,5)P3.
Decapitation also induced an increase in the levels of DGs and FFAs. Unlike the transient appearance of Ins(1,4,5)P3, however, DG levels increased steadily for 2 min and then reached a plateau whereas the FFAs showed a lag time of 35 s prior to a biphasic increase. During the initial 2 min after
decapitation, there was a preferential increase in the DG species containing 18:0 and 20:4.
Lithium administration did not alter the
decapitation-induced release of DG and FFA. As expected,
decapitation gave rise to a rapid decrease in the levels of
phosphocreatine and
ATP and the decline in
ATP was marked by a transient appearance of
ADP and a concomitant increase in
AMP.(ABSTRACT TRUNCATED AT 250 WORDS)