Yang S G, Saifeddine M, Chuang M, Severson D L, Hollenberg M D
Department of Pharmacology and Therapeutics, University of Calgary, Faculty of Medicine, Alberta, Canada.
Eur J Pharmacol. 1991 Jul 12;207(3):225-30. doi: 10.1016/0922-4106(91)90034-f.
In guinea pig gastric longitudinal muscle preparations, wherein epidermal growth factor-urogastrone (EGF-URO) causes contraction via the generation of arachidonate-derived prostaglandins, the specific diacylglycerol lipase (DG lipase) inhibitor, U57,908 (formerly designated RHC 80267) completely blocked EGF-URO and transforming growth factor-alpha (TGF-alpha)-mediated contraction, without affecting contractions caused by other agonists such as bradykinin, prostaglandin F2 alpha or arachidonic acid (AA). In contrast, the contractile actions of EGF-URO and TGF-alpha on the gastric circular muscle component, present in the same tissue strip as the longitudinal muscle preparation, were unaffected by concentrations of U57,908 that maximally inhibited contraction in the longitudinal muscle preparation. We conclude that in the longitudinal muscle preparation, EGF-URO acts not by the activation of phospholipase A2, but rather via the metabolism of diacylglycerol by DG lipase, thereby liberating arachidonic acid for the synthesis of contractile prostanoids. We also conclude that, even in the same tissue, the effects of EGF-URO on anatomically different components (longitudinal muscle versus circular muscle) can be mediated via two quite distinct signal transduction pathways.
在豚鼠胃纵肌制备物中，表皮生长因子-尿抑胃素（EGF-URO）通过生成花生四烯酸衍生的前列腺素引起收缩，特异性二酰基甘油脂肪酶（DG脂肪酶）抑制剂U57,908（原称RHC 80267）完全阻断EGF-URO和转化生长因子-α（TGF-α）介导的收缩，而不影响由其他激动剂如缓激肽、前列腺素F2α或花生四烯酸（AA）引起的收缩。相反，EGF-URO和TGF-α对与纵肌制备物存在于同一组织条中的胃环肌成分的收缩作用，不受在纵肌制备物中最大程度抑制收缩的U57,908浓度的影响。我们得出结论，在纵肌制备物中，EGF-URO的作用不是通过激活磷脂酶A2，而是通过DG脂肪酶对二酰基甘油的代谢，从而释放花生四烯酸用于合成收缩性前列腺素。我们还得出结论，即使在同一组织中，EGF-URO对解剖学上不同成分（纵肌与环肌）的作用也可通过两条截然不同的信号转导途径介导。
