Gorini A, Villa R F
Department of Physiological-Pharmacological Cellular-Molecular Sciences, University of Pavia, Italy.
Neurochem Res. 2001 Jul;26(7):821-7. doi: 10.1023/a:1011616219687.
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.
在大鼠大脑皮层的两种突触质膜中，研究了体内注射可乐定后对耗能ATP酶的影响。为了在亚细胞水平研究可乐定的作用机制，对对照组和用可乐定（5μg·kg⁻¹；腹腔注射30分钟）处理的动物的突触质膜上的Na⁺、K⁺-ATP酶、Ca²⁺、Mg²⁺-ATP酶、低亲和力和高亲和力Ca²⁺-ATP酶以及Mg²⁺-ATP酶的酶活性进行了评估。可乐定的急性处理仅降低了II型突触质膜（即富含突触质膜的部分）中Ca²⁺、Mg²⁺-ATP酶和低亲和力Ca²⁺-ATP酶的催化活性。这些酶活性的降低与药物对突触浆中Ca²⁺稳态的干扰有关。这些消耗ATP的酶的减少进一步证明可乐定不仅具有神经受体效应，而且该药物还影响脑组织的能量代谢，增进了对可乐定药理学的认识。由于缺血/缺氧期间细胞内Ca²⁺浓度升高会导致细胞损伤，这些发现可能表明预防钙超载可能是α₂激动剂保护作用的关键机制。
