Effect of in vivo treatment of clonidine on ATP-ase's enzyme systems of synaptic plasma membranes from rat cerebral cortex.
The effects on energy-consuming ATP-ases were studied in two types of synaptic plasma membranes from rat cerebral cortex after in vivo injection of clonidine. To study the mechanism of action of clonidine at subcellular level, the enzyme activities of Na+, K+-ATP-ase, Ca2+, Mg2+-ATP-ase, Low- and High-affinity Ca2+-ATP-ase, and Mg2+-ATP-ase were evaluated on synaptic plasma membranes of control and treated animals with clonidine (5 microg x kg(-1); i.p. 30 minutes). Acute treatment with clonidine decreased the catalytic activity of Ca2+, Mg2+-ATP-ase and of low-affinity Ca2+-ATP-ase only in synaptic plasma membranes of II type, that is the fraction enriched in synaptic plasma membranes. The decreases of these enzymatic activities are related to the interference of the drug on Ca2+ homeostasis in synaptoplasm. The reductions of these enzyme-consuming ATP-ases give further evidence that clonidine has not only neuroreceptorial effects, but that the drug also affects the energy metabolism of cerebral tissue, improving the knowledges about the pharmacology of clonidine. Because the elevation of [Ca2+]i, during ischemia/hypoxia contributes to cellular injury, these findings may suggest that the prevention of calcium overload may be the key mechanism of protection by alpha2-agonist.
Gorini
A
A
Department of Physiological-Pharmacological Cellular-Molecular Sciences, University of Pavia, Italy.
Villa
R F
RF
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D003000:Clonidine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects / Q000201:enzymology*
D000316:Adrenergic alpha-Agonists; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D003000:Clonidine