Neurochemical Research, VoL 19, No. 4, 1994, pp. 517-524 Modifications by Hypoxia and Drug Treatment of Cerebral ATPase Plasticity Gianni Benzi, 1,2 Antonella Gorini, 1 Barbara Ghigini, ~ Roberto Arnaboldi, 1 and Roberto F. Villa ~ (Accepted November 30, 1993) The plasticity of synaptosomal non-mitochondrial ATPases was evaluated in cerebral cortex from 3-month-old normoxic rats and rats subjected to either mild or severe intermittent normobaric hypoxia [12 hr daily exposure to N2:O: (90:10 or 91.5:8.5) for four weeks]. The activities of Na +, K+-ATPase, low- and high-affinity Ca2+-ATPase, Mg2+-ATPase, and Ca2+,Mga+-ATPase were assayed in synaptosomes and synaptosomal subfractions, namely synaptosomal plasma membranes and synaptic vesicles. The evaluations were performed after a 4-week treatment with saline (con- trols) or cx-adrenergic agents (8-yohimbine, clonidine), a vasodilator compound (papaverine), and an oxygen-partial pressure increasing agent (almitnne). These treatments differently changed the adaptation to chronic intermittent hypoxia characterized by a decrease in the activity of Na+,K +- ATPase, Ca2+,Mga+-ATPase, and high-affinity Caa+-ATPase, concomitant with a modification in the activity of MgZ+-ATPase supported in a different way by the enzymatic forms located into the synaptosomal plasma membranes and synaptic vesicles. KEY WORDS: Almitrine; ATPase plasticity; clonidine; 8-yohimbine; papaverine; synaptosomes. INTRODUCTION The plasticity of cerebral enzyme proteins may be carefully studied by means of the chronic sequential cycles of hypoxia/normoxia inducing alternative conditions of either absolute hypoxemia or relative hyperoxemia char- acterized by some adaptive modifications, namely: change in the composition of specific proteins in synaptosomal plasma membranes from cerebral cortex (1); decrease in the incorporation of labeled precursor into deoxyribo- nucleic acid, ribonucleic acid, proteins and lipids in subfractions from different brain regions (2,3); activa- tion of cerebral mitochondrial phospholipase A2 (4); se- lective alterations of enzymes having different half-lives 1 Institute of Pharmacology-State University of Pavia (Italy). a Address reprint requests to: Prof. Gianni Benzi MD, PhD, Istituto di Farmacologia, Universit?~ di Pavia, 11, Piazza Botta, 1-27100 Pa- via, Italia. tel. (39) [382] 386.381 fax (39) [382] 386.385 517 (5); decrease in cytochrome oxidase and malate dehy- drogenase activities in synaptosomal fraction from dif- ferent brain regions (6). The non-mitochondrial synaptic ATPases [namely, Na+,K+-ATPase, low- and high-affinity Ca2+-ATPase, Mg2+-ATPase and Ca 2+, Mg2+-ATPase] are affected by hypoxia and post-hypoxic recovery (7-11), the Ca a+ in- ducing membrane phospholipase stimulation (12-14), xanthine oxidase activation (13,15), and metabolic en- zyme system alteration (16). The synaptic ATPases modulate the presynaptie nerve ending homeostasis. Na+,K+-ATPase is located in the synaptic plasma mem- branes and functions as an electrogenic Na+/K+-pump that maintains a low intracellular Na § concentration and Na § and K + gradients (17-20). This pump modulates the resting transmembrane potential (21), some postsyn- aptic activities (22,23) and the transmitter turnover (24- 28). Synaptic low- and high-affinity Mgi+-independent 0364-3190/94/0400-0517507.00/0 91994Plenum Publishing Corporation