Sun L, Philipson L H, Miller R J
Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, Illinois 60637, USA.
J Pharmacol Exp Ther. 1998 Feb;284(2):625-32.
We examined the ability of rat Y1, Y2 and Y4 neuropeptide Y (NPY) receptors to regulate K+ and Ca++ channels expressed in Xenopus oocytes and HEK 293 cells, respectively. Stimulation of all three receptors with NPY or related peptides activated inwardly rectifying K+ currents resulting from the expression of rat GIRK1/CIR in frog oocytes. These effects were inhibited by pertussis toxin treatment. The effects of activating Y1 receptors were antagonized competitively by BIBP3226, SR120819A and GW1229. The effects of Y2 receptor activation were not blocked by these drugs, and the effects of Y4 receptor activation were only blocked by GW1229. Activation of all three NPY receptors also inhibited human alpha-1B Ca++ channels stably expressed in HEK293 cells. The effects of agonists at all three receptors were blocked by pertussis toxin treatment and were voltage dependent. Activation of all three types of NPY receptors produced much smaller inhibition of human alpha-1E Ca++ channels also stably expressed in HEK293 cells. These results suggest that NPY receptors can regulate K+ and Ca++ channels and that these effects may be responsible for the observed effects of NPY on neuronal excitability and synaptic transmission.
我们分别研究了大鼠Y1、Y2和Y4神经肽Y（NPY）受体调节非洲爪蟾卵母细胞和人胚肾293（HEK 293）细胞中表达的钾离子（K+）通道和钙离子（Ca++）通道的能力。用NPY或相关肽刺激所有这三种受体，可激活由大鼠GIRK1/CIR在蛙卵母细胞中表达所产生的内向整流钾电流。这些效应可被百日咳毒素处理所抑制。BIBP3226、SR120819A和GW1229可竞争性拮抗激活Y1受体的效应。激活Y2受体的效应不受这些药物的阻断，而激活Y4受体的效应仅被GW1229阻断。激活所有这三种NPY受体也可抑制稳定表达于HEK293细胞中的人α-1B钙离子通道。所有这三种受体的激动剂的效应可被百日咳毒素处理所阻断，且具有电压依赖性。激活所有这三种类型的NPY受体对同样稳定表达于HEK293细胞中的人α-1E钙离子通道产生的抑制作用要小得多。这些结果表明，NPY受体可调节钾离子通道和钙离子通道，且这些效应可能是NPY对神经元兴奋性和突触传递的观察到的效应的原因。
