BETA-ADRENERGIC-RECEPTOR AGONISTS INCREASE PHOSPHOLIPID METHYLATION, MEMBRANE FLUIDITY, AND BETA-ADRENERGIC RECEPTOR-ADENYLATE CYCLASE COUPLING
BETA-ADRENERGIC-RECEPTOR AGONISTS INCREASE PHOSPHOLIPID METHYLATION, MEMBRANE FLUIDITY, AND BETA-ADRENERGIC RECEPTOR-ADENYLATE CYCLASE COUPLING
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DOI：
10.1073/pnas.76.1.368
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发表时间：
1979-01-01
影响因子：
11.1
通讯作者：
AXELROD, J
中科院分区：
文献类型：
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作者：
HIRATA, F;STRITTMATTER, WJ;AXELROD, J
β-肾上腺素能激动剂L-异丙肾上腺素可刺激含有甲基供体S-腺苷-L-蛋氨酸的大鼠网织红细胞幽灵中磷脂酰乙醇胺和磷脂酰胆碱的酶合成。这种刺激是立体特异性的，呈剂量依赖性，并被β-肾上腺素能激动剂心得安抑制。GTP的加入使L-异丙肾上腺素所致磷脂甲基化的量效关系左移2个数量级。用NaF或霍乱毒素直接刺激腺苷环化酶[ATP焦磷酸裂解酶(环化)，EC 4.6.1.1]并不增加磷脂甲基化。在刺激磷脂酰N-甲基乙醇胺合成的S-腺苷-L-蛋氨酸浓度下，腺苷环化酶的活性增加2倍，而腺苷环化酶的基础活性和β-肾上腺素能受体的数目不变。L-异丙肾上腺素增加了磷脂甲基化，降低了膜粘度，增加了甲基化脂质的转运。这些结果表明，L-异丙肾上腺素促进磷脂甲基化，使膜微粘度降低，从而增加β-肾上腺素能受体的侧向运动，并与腺苷环化酶偶联。
The .beta.-adrenergic agonist L-isoproterenol stimulated the enzymic synthesis of phosphatidyl-N-monomethylethanolamine and phosphatidylcholine in rat reticulocyte ghosts containing the methyl donor S-adenosyl-L-methionine. The stimulation was stereospecific, dose-dependent, and inhibited by .beta.-adrenergic agonist propranolol. The addition of GTP inside the resealed ghosts shifted the dose-response of phospholipid methylation by L-isoproterenol to the left by 2 orders of magnitude. Direct stimulation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] with NaF or cholera toxin did not increase the methylation of phospholipids. At a concentration of S-adenosyl-L-methionine that stimulates synthesis of phosphatidyl-N-monomethylethanolamine, the activity of sioproterenol-sensitive adenylate cyclase was increased 2-fold without changes in the basal activity of adenylate cyclase and the number of .beta.-adrenergic receptors. The increase of phospholipid methylation by L-isoproterenol decreased membrane viscosity and increased translocation of methylated lipids. These findings indicate that enhancement of phospholipid methylation by L-isoproterenol decreases membrane microviscosity and thus increases lateral movement of the .beta.-adrenergic receptors and coupling with adenylate cyclase.