Chern Y J, Bott M, Chu P J, Lin Y J, Kao L S, Westhead E W
Program in Molecular and Cellular Biology, University of Massachusetts, Amherst.
J Neurochem. 1992 Oct;59(4):1399-404. doi: 10.1111/j.1471-4159.1992.tb08453.x.
We reported earlier that adenine nucleotides and adenosine inhibit acetylcholine-induced catecholamine secretion from bovine adrenal medulla chromaffin cells. In this article, we used an adenosine analogue, N6-L-phenylisopropyladenosine (PIA), to study the mechanism underlying inhibition of catecholamine secretion by adenosine. PIA inhibits secretion induced by a nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium, or by elevated external K+. The half-maximal effect on 1,1-dimethyl-4-phenylpiperazinium-induced secretion occurred at approximately 5 x 10(-5) M. The inhibition is immediate and reversible. Fura-2 measurements of cytosolic free Ca2+ indicate that PIA inhibits Ca2+ elevation caused by stimulation; measurements of 45Ca2+ influx show that PIA inhibits uptake of Ca2+. PIA does not inhibit calcium-evoked secretion from digitonin-permeabilized cells, nor does PIA cause any significant change in the dependence of catecholamine secretion on calcium concentration. These data suggest that inhibition by PIA occurs at the level of the voltage-sensitive calcium channel.
我们先前报道过，腺嘌呤核苷酸和腺苷可抑制乙酰胆碱诱导的牛肾上腺髓质嗜铬细胞分泌儿茶酚胺。在本文中，我们使用一种腺苷类似物，N6-L-苯基异丙基腺苷（PIA），来研究腺苷抑制儿茶酚胺分泌的潜在机制。PIA可抑制由烟碱激动剂1,1-二甲基-4-苯基哌嗪或细胞外高钾诱导的分泌。对1,1-二甲基-4-苯基哌嗪诱导分泌的半数最大效应出现在约5×10⁻⁵ M。这种抑制作用迅速且可逆。用Fura-2测量细胞质游离Ca²⁺表明，PIA可抑制刺激引起的Ca²⁺升高；测量⁴⁵Ca²⁺内流表明，PIA可抑制Ca²⁺摄取。PIA并不抑制从洋地黄皂苷通透细胞中钙诱发的分泌，PIA也不会使儿茶酚胺分泌对钙浓度的依赖性发生任何显著变化。这些数据表明，PIA的抑制作用发生在电压敏感性钙通道水平。
