Effects of oxygen depletion on norepinephrine- and carbachol-stimulated phosphoinositide turnover in rat brain slices.
We examined the effects of in vitro anoxia and in vivo hypoxia (8% O2/92% N2) on norepinephrine (NE)- and carbachol-stimulated phosphoinositide (PI) turnover in rat brain slices. The formation of 3H-labeled polyPI in cortical slices was impaired by in vitro anoxia and fully restored by reoxygenation. Accumulation of 3H-labeled myo-inositol phosphates (3H-IPs) stimulated by 10(-5) M NE was significantly reduced by anoxia (control at 60 min, 1,217 +/- 86 cpm/mg of protein; anoxia for 60 min, 651 +/- 82 cpm/mg; mean +/- SEM; n = 5; p less than 0.01), and reoxygenation following anoxia resulted in overshooting of the accumulation (control at 120 min, 1,302 +/- 70 cpm/mg; anoxia for 50 min plus oxygenation for 70 min, 1,790 +/- 126 cpm/mg; n = 5; p less than 0.01). The underlying mechanisms for the two phenomena--the decrease caused by anoxia and the overshooting caused by reoxygenation following anoxia--seemed to be completely different because of the following observations. (a) Although the suppression of NE-stimulated accumulation at low O2 tensions was also observed in Ca2+-free medium, the overshooting in response to reoxygenation was not. (b) Carbachol-stimulated accumulation was significantly reduced by anoxia and was restored by reoxygenation only to control levels. Thus, the postanoxic overshooting in accumulation of 3H-IPs seems to be a specific response to NE. (c) The decrease observed at low O2 tensions was due to a decrease in Emax value, whereas the postanoxic overshooting was due to a decrease in EC50 value.(ABSTRACT TRUNCATED AT 250 WORDS)
Ninomiya
H
H
Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
Taniguchi
T
T
Fujiwara
M
M
Kameyama
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D014018:Tissue Distribution
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010743:Phospholipids; D007294:Inositol; D002217:Carbachol; D010100:Oxygen; D009638:Norepinephrine