Brain ischemia in gerbils was induced by
ligation of both common carotid arteries for 1 min or 10 min.
Sham-operated animals served as controls. Intracerebral injection of [3H]
inositol into gerbil brain 16 hr before ischemic insult resulted in equilibration of the label between
inositol lipids and water-soluble
inositol phosphate. A short ischemic period (1 min) resulted in a statistically significant increase in the radioactivity of
inositol triphosphate (IP3) and
inositol monophosphate (IP), by about 48% and 79%, respectively, with little change in that of the intermediate
inositol biphosphate (IP2), which increased by about 16%. When the ischemic period was prolonged (10 min), an increase in the radioactivity of
inositol monophosphate exclusively, by about 84%, was observed. The level of radioactivity in
inositol phosphates IP2 and IP3 decreased by about 50%, probably as a consequence of
phosphatase activation by the ischemic insult. The agonist of the
cholinergic receptor,
carbachol, injected intracerebrally (40 micrograms per animal) increased accumulation of radioactivity in all
inositol phosphates. The level of radioactivity in IP3, IP2, and IP was elevated by about 40, 23, and 147%, respectively. The
muscarinic cholinergic antagonist,
atropine, injected intraperitoneally in doses of 100 mg/kg body wt. depressed
phosphoinositide metabolism in control animals. The level of radioactivity in water-soluble
inositol metabolites in the brain of animals pretreated with
atropine was evidently about 32% lower than in untreated animals. Pretreatment with
atropine decreased the radioactivity of all
inositol phosphates in the brain of animals subjected to 1-min
ischemia and the radioactivity of IP in the case of 10-min
brain ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)