血管收縮素促進腎臟水分再吸收作用及血管收縮之功能為眾所周知。在最近的報導上，指出了血管收縮素及其受體在小細胞肺癌及乳癌有基因表現的現象。血管收縮素此神經鏈及其受體在癌症病因學上扮演之角色，始終不甚清楚。我們目前利用反轉錄聚合反應，來瞭解正常肺細胞株中(MRC-5)及小細胞肺癌(H-209)中，血管收縮素此神經鏈及其受體之基因表現。另外，我們探討血管收縮素在正常肺細胞株是否進行正常之訊息傳遞路徑。由我們初步之反轉錄聚合反應結果顯示，血管收縮素此神經鏈及其第一亞型受體在這兩株肺細胞中並無表現，但血管收縮素第二亞型受體可被偵測。利用環腺甘酸分析組套，分析經過血管收縮素刺激之後，在MRC-5細胞中，環腺甘酸之含量是否上升。我們無法偵測出環腺甘酸含量之上升，表示血管收縮素在MRC-5細胞中並未進行第二亞型受體驅動之正常訊息傳遞路徑。但在同時，用前列腺素E2去刺激MRC-5細胞，環腺甘酸之含量卻大幅上升，顯示前列腺素E2在MRC-5細胞株其下游之訊息路徑是可行的。我們利用反轉錄聚合反應，偵測出第四亞型之前列腺素E2受體是存在於MRC-5細胞中最主要之前列腺素E2受體。我們也同時研究煙草中之致癌物，Benzopyrene，對血管收縮素及相關神經鏈在此二株細胞中之基因表現。我們發現，在MRC-5中，全然無血管收縮素及其他神經鏈之基因表現。但在H-209中，雖無AVP及Vla receptor之基因表現，但卻有V2 receptor、CCK-B以及GRP此二神經鏈之基因表現。然而，使用不同濃度之Benzopyrene，分別處理不同時間卻看不到V2 receptor、CCK-B以及GRP在基因表現上有何差異。Benzopyrene對V2 receptor、CCK-B以及GRP在H-209中之基因表現可能並無直接影響。
The roles of arginine vasopressin (AVP) in regulating water retention and vasoconstriction in kidney is well-defined. Despite recent reports on expression of genes coded for AVP and its receptors in small cell lung carcinoma (SCLC) and breast cancer (Ref. l~3), the roles of the neuropeptides and the receptors in cancer etiology are unclear. Therefore, we propose to investigate signaling pathway involving AVP and its receptors in SCLC (H-209) as compared with a normal lung cell line (MRC-5). Using RT-PCR, the gene expression of AVP and its receptors were investigated in these two cell lines. Only V2 receptor was detectable in both cell lines, the AVP and V1a receptors were undetectable. The cAMP signaling in MRC-5 cells triggered by AVP was determined. No detectable cAMP level was increased after AVP stimulation compared with the untreated cells. This indicated the V2 receptor signaling pathway was not function well in MRC-5 cells even the V2 receptor was expressed in MRC-5 cells. On the other hand, when PGE2 was added in MRC-5 cells, the cAMP level was increased beyond 1000 times compared with the basal level of untreated cells. EP4 was the major PGE2 receptor in MRC-5 cells as detected by RT-PCR. The effect of benzopyrene on the gene expression of AVP and other neuropeptides was investigated in both cell lines. Although V2 receptor was detected in MRC-5 cell, AVP, V1a receptor and other neuropeptides were undetectable. On the other hand, in H-209 cells, although AVP and V1a receptor was undetectable, V2 receptor, CCK-B and GRP were detected. The gene expression of V2 receptor, CCK-B and GRP in H-209 cells were not altered when treated with different doses of benzopyrene with different time. Benzopyrene may not have direct effect on the gene expression of V2 receptor, CCK-B and GRP in H-209 cells.
