Lawrence A J, Castillo-Meléndez M, Jarrott B
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Neurochem Int. 1994 Sep;25(3):221-6. doi: 10.1016/0197-0186(94)90065-5.
The neuromodulator adenosine, has been shown to have the highest density of central uptake sites in the nucleus tractus solitarius in the dorsal brain stem. The nucleus tractus solitarius is involved in the central regulation of reflex cardiovascular activity suggesting that adenosine may also be involved in central cardiovascular control. Thus, the present study has characterized the transport of [3H]adenosine into rat dorsal brain stem synaptosomes. The process was found to be saturable and highly dependent on temperature. Furthermore, [3H]adenosine transport in rat dorsal brain stem synaptosomes was far more sensitive to the removal of sodium ions than has been previously reported for rat cortical synaptosomes. In addition transport was rapid, being linear for at least 30 s at 37 degrees C, reaching equilibrium within 1 min and had an apparent Km value of 2.7 +/- 0.2 microM (n = 4) and a Vmax value of 135.5 +/- 17.8 pmol/mg protein/min (n = 4). These kinetic parameters are within an order of magnitude of adenosine uptake processes found in rat cerebral cortical synaptosomes. Transport of [3H]adenosine was significantly inhibited by an excess of unlabelled adenosine (1 mM) and the adenosine uptake inhibitor S(4-nitrobenzyl)-6-thioinosine (100 microM) while morphine (150 microM) and flurazepam (150 microM) were largely ineffective as inhibitors of the process, in contrast with previous findings in rat cortical synaptosomes. The present findings demonstrate the presence of a high affinity transport system for adenosine in the rat dorsal brain stem which appears to differ in some properties to uptake processes found in rat cortex.
神经调质腺苷在延髓背侧孤束核中的中枢摄取位点密度最高。孤束核参与反射性心血管活动的中枢调节,这表明腺苷可能也参与中枢心血管控制。因此,本研究对[3H]腺苷向大鼠延髓背侧脑干突触体的转运进行了特性描述。发现该过程具有饱和性且高度依赖温度。此外,大鼠延髓背侧脑干突触体中[3H]腺苷的转运对钠离子去除的敏感性远高于先前报道的大鼠皮质突触体。另外,转运速度很快,在37℃下至少30秒呈线性,1分钟内达到平衡,其表观Km值为2.7±0.2微摩尔(n = 4),Vmax值为135.5±17.8皮摩尔/毫克蛋白/分钟(n = 4)。这些动力学参数与大鼠大脑皮质突触体中腺苷摄取过程的参数在一个数量级内。过量的未标记腺苷(1毫摩尔)和腺苷摄取抑制剂S(4-硝基苄基)-6-硫代肌苷(100微摩尔)可显著抑制[3H]腺苷的转运,而吗啡(150微摩尔)和氟西泮(150微摩尔)作为该过程的抑制剂基本无效,这与先前在大鼠皮质突触体中的发现不同。目前的研究结果表明,大鼠延髓背侧脑干中存在一种高亲和力的腺苷转运系统,其某些特性似乎与大鼠皮质中的摄取过程不同。