Phamracological and molecular biological analyzes on regulatory mechanisms for neurotransmitter receptor expression

点击翻译按钮获取中文摘要

Regulatory mechanisms for exoression of neurotransmitter receptors, especially beta-adrenergic receptors ( beta-AR), were investigated by measuring [^3H] CGP-12177 binding to the particulate fraction from mouse cerebral cortical neurons and mRNAs of beta1-and beta2-AR in neurons exposed to nadolol, an antagonist of beta-AR.Nadolol exposure induced rapid increase in the binding within 12 hrs and the binding attained its plateau after 24 hrs of the exposure. When measuring [^3H] CGP-12177 binding in the presence of each antagonist for beta2-and beta1-AR,the bindings significantly increased, indicating that the bindings to both beta1-and beta2-AR increased. Scatchard analysis revealed that this increase in the binding was due to Bmax balue without any changes in Kd value. mRNAs for both beta-AR subtypes increased significantly 24 hrs after the exposure, suggesting two distinct processers, increasing processer of receptor number with and without increase in mRNA.After 15 min and 1 hr of the exposure significant and transient increases in zif286 and c-fos mRNAs were observed. Induction of antisense for zif286 into the neurons before the exposure to nadolol abolished nadolol-induced increase in [^3H] CGP-12177 binding. These results indicate that the expression of zif286 plays a significant role in the expression of beta-AR upregulation. Inaddition, released of GABA release mechanisms by nitric oxide (NO) were investigated. Both materials induced increases in GABA release both dependent on Ca^<2+> and independent of Ca^<2+>. The latter type of release was the reverse process of Na^+-dependent GABA transport system. The increased influx Ca^<2+> of by NO is clarified to be caused by activation of L-and P/Q-typed voltage-dependent Ca^<2+> channels.