Brown L A, Chen M
Department of Pediatrics, Emory University, Atlanta, Georgia.
Am J Physiol. 1990 Jun;258(6 Pt 1):L301-7. doi: 10.1152/ajplung.1990.258.6.L301.
Previous studies demonstrate that in cultured type II pneumocytes, [Arg8]-vasopressin (AVP) stimulates surfactant secretion independent of adenosine 3',5'-cyclic monophosphate (cAMP). In the current study AVP stimulated a 50% loss of radioactive phosphatidylinositol 4,5-bisphosphate (PIP2) within 15 s. Consistent with AVP-induced PIP2 hydrolysis was an increased appearance of the two breakdown products 1,2-diacylglycerol (1,2-DAG) and inositol 1,4,5-trisphosphate (IP3). Also, AVP stimulated the appearance of radiolabel in phosphatidic acid (PA) suggesting that the conversion of 1,2-DAG to PA could be used for PIP2 resynthesis. The effects of AVP on PIP2 and IP3 were mimicked by the bioactive AVP fragment and inhibited by the specific AVP1 antagonist. The EC50 for AVP on IP3 production was 6 nM. AVP stimulated protein kinase C (PK-C) activity twofold over the basal activity of 0.74 +/- 0.07 nmol P.min-1.mg protein-1 but did not activate cAMP-dependent protein kinase activity. The AVP1 antagonist inhibited AVP activation of PK-C. Therefore, activation of the AVP1 receptor resulted in PIP2 hydrolysis for signal transduction, PK-C activation, and surfactant secretion.
先前的研究表明，在培养的II型肺细胞中，[精氨酸8] - 血管加压素（AVP）刺激表面活性剂分泌，且不依赖于3',5'-环磷酸腺苷（cAMP）。在当前研究中，AVP在15秒内使放射性磷脂酰肌醇4,5-二磷酸（PIP2）损失了50%。与AVP诱导的PIP2水解一致的是，两种分解产物1,2-二酰基甘油（1,2-DAG）和肌醇1,4,5-三磷酸（IP3）的出现增加。此外，AVP刺激了磷脂酸（PA）中放射性标记的出现，这表明1,2-DAG向PA的转化可用于PIP2的再合成。AVP对PIP2和IP3的作用被生物活性AVP片段模拟，并被特异性AVP1拮抗剂抑制。AVP对IP3产生的EC50为6 nM。AVP使蛋白激酶C（PK-C）活性比基础活性0.74±0.07 nmol P·min-1·mg蛋白-1增加了两倍，但未激活cAMP依赖性蛋白激酶活性。AVP1拮抗剂抑制了AVP对PK-C的激活。因此，AVP1受体的激活导致PIP2水解以进行信号转导、PK-C激活和表面活性剂分泌。
