Effect of atropine and gammahydroxybutyrate on ischemically induced changes in the level of radioactivity in [3H]inositol phosphates in gerbil brain in vivo.
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)
Wikieł
H
H
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warsaw.
Halat
G
G
Strosznajder
J
J
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002545:Brain Ischemia / Q000378:metabolism*; D005849:Gerbillinae; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism*; D012978:Sodium Oxybate / Q000494:pharmacology*; D012995:Solubility; D013403:Sugar Phosphates / Q000378:metabolism*; D014316:Tritium; D014867:Water
D006885:Hydroxybutyrates; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D014867:Water; D014316:Tritium; D001285:Atropine; D012978:Sodium Oxybate