α- and β-adrenergic stimulation of arachidonic acid metabolism in cells in culture
α- and β-adrenergic stimulation of arachidonic acid metabolism in cells in culture
复制标题
培养细胞中花生四烯酸代谢的α-和β-肾上腺素刺激
DOI：
10.1073/pnas.76.12.6632
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发表时间：
1979
影响因子：
11.1
通讯作者：
M. Moskowitz
中科院分区：
文献类型：
--
作者：
L. Levine;M. Moskowitz
摘要
Madin-Darby犬肾细胞（MDCK）合成前列腺素（PG）F2α、PGI 2（以6-酮-PGE 1 α计）、PGE 2、PGD 2和血栓烷A2（以血栓烷B2计）。当在存在去甲肾上腺素（6 μM）的情况下孵育时，这些花生四烯酸代谢物的合成被刺激3倍。去甲肾上腺素的作用可以通过添加α-肾上腺素能受体阻滞剂（酚苄明>酚妥拉明>育亨宾>二苯拉明>妥拉唑林）来拮抗，但不能通过β-肾上腺素能阻滞剂普萘洛尔来拮抗。去甲肾上腺素的刺激也被低浓度的二氢麦角胺、溴隐亭、麦角隐亭和麦角胺抑制。去甲肾上腺素对PG合成的刺激是可逆的，在孵育的24小时期间持续，并且需要在受体位点存在去甲肾上腺素，但它不被秋水仙碱、细胞松弛素B或放线菌酮阻断。在阻断去甲肾上腺素对PG生物合成的刺激的浓度下，酚苄明和麦角胺都不能抑制外源性花生四烯酸诱导的PG合成的增加，这表明α-肾上腺素能调节主要不是发生在花生四烯酸代谢中的环氧合酶步骤。在小鼠淋巴瘤细胞（WEHI-5）中，低浓度的异丙肾上腺素或去甲肾上腺素刺激血栓素的合成，这种作用可以通过加入普萘洛尔而不是通过相对高浓度的酚苄明或麦角胺来阻断。总之，这些结果表明，α-肾上腺素能受体刺激促进MDCK细胞磷脂的脱酰化，而β-肾上腺素能机制导致WEHI-5细胞中类似途径的激活。
Abstract
Madin—Darby canine kidney cells (MDCK) synthesize prostaglandin (PG) F2α, PGI2 (measured as 6-keto-PGE1α), PGE2, PGD2, and thromboxane A2 (measured as thromboxane B2). When incubated in the presence of norepinephrine (6 μM), the syntheses of these arachidonic acid metabolites are stimulated 3-fold. Norepinephrine's effect can be antagonized by the addition of α-adrenergic receptor blocking agents (phenoxybenzamine>phentolamine>yohimbine>dibenamine>tolazoline) but not by the β-adrenergic blocking drug propranolol. Norepinephrine's stimulation is also inhibited by low concentrations of dihydroergotamine, bromocryptine, ergocryptine, and ergotamine. The stimulation of PG synthesis by norepinephrine is reversible, continues during the 24 hr of incubation, and requires the presence of norepinephrine at the receptor site but it is not blocked by the addition of colchicine, cytochalasin B, or cycloheximide. Neither phenoxybenzamine nor ergotamine at concentrations that block norepinephrine's stimulation of PG biosynthesis suppresses the increase in PG synthesis induced by exogenous arachidonic acid, suggesting that the α-adrenergic regulation is not occurring primarily at the cyclooxygenase step in the metabolism of arachidonic acid. In mouse lymphoma cells (WEHI-5), low concentrations of isoproterenol or norepinephrine stimulate the synthesis of thromboxane, an effect that can be blocked by the addition of propranolol but not by relatively high concentrations of phenoxybenzamine or ergotamine. Taken together, these results suggest that α-adrenergic receptor stimulation promotes the deacylation of phospholipids by MDCK cells whereas β-adrenergic mechanisms lead to activation of similar pathways in WEHI-5 cells.