title: Effect of in vivo exposure to hypoxia on muscarinic cholinergic receptor-coupled phosphoinositide turnover in the rat brain.
abstract: We examined the effects of a transient exposure of rats to severe (5% O2, 95% N2 for 30 min) or mild (10% O2, 90% N2 for 30 min) hypoxia and a chronic exposure to mild hypoxia (10% O2, 90% N2 up to 48 h) on carbachol-stimulated phosphoinositide (PI) turnover and [3H]quinuclidinyl benzilate (QNB) binding in 4 regions of the brain (cerebral cortex, striatum, hippocampus and cerebellum). When the rats were exposed to hypoxia transiently, significant changes were caused only by severe hypoxia. In all 4 regions examined, basal incorporation of [3H]inositol into inositol phosphates (IPs) in the absence of carbachol was significantly increased following transient severe hypoxia and remained high for 48 h. Carbachol stimulation of PI turnover (% of basal) was significantly enhanced only in the hippocampus. The increase in carbachol stimulation in the hippocampus was observed only after a 6-h exposure to room air following the severe hypoxia and lasted for at least 48 h. In Ca2+-free incubation medium, the increase in basal incorporation of [3H]inositol into IPs elicited by severe hypoxia was not observed but carbachol still had an enhanced stimulatory effect. Binding studies showed that maximum binding capacity (Bmax values) of [3H]QNB binding was significantly increased only in the hippocampus and only after a 6-h exposure to room air following the severe hypoxic exposure and remained increased for 48 h. Kd values showed no significant change. While a transient exposure of rats to mild hypoxia caused no significant change either in carbachol-stimulated PI turnover or in [3H]QNB binding parameters, a chronic exposure to mild hypoxia for more than 6 h caused a significant increase in [3H]QNB binding capacity localized in the hippocampus, which was accompanied by an enhanced stimulatory effect of carbachol on PI turnover. These changes observed with mild hypoxia, however, were transient and tended to return to control levels following a 48-h exposure. These results suggest an up-regulation of muscarinic cholinergic receptor-coupled PI turnover in the rat brain caused either by transient severe hypoxia or by chronic mild hypoxia.
authors.affiliation: Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ninomiya
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: M
authors.initials: M
authors.lastname: Fujiwara
authors.forename: S
authors.initials: S
authors.lastname: Shimohama
authors.forename: M
authors.initials: M
authors.lastname: Kameyama
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000378:metabolism*; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D002217:Carbachol