Sakamoto C, Matozaki T, Nagao M, Nishisaki H, Baba S
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Pancreas. 1988;3(1):18-24. doi: 10.1097/00006676-198802000-00004.
Labeled somatostatin binding to pancreatic acinar membranes was examined to investigate how pancreatic secretagogues regulate somatostatin receptors in the pancreas. Pretreatment of pancreatic acini at 37 degrees C for 120 min with not only pancreatic secretagogues, such as carbachol and bombesin, but also vasoactive intestinal peptide (VIP) and secretin reduced subsequent labeled somatostatin binding to the acinar membranes in a dose-dependent manner. The inhibitory effects of these secretagogues on labeled somatostatin binding were also time dependent. Both types of secretagogues maximally reduced subsequent somatostatin binding when acini were incubated with them for more than 120 min. However, the degree of the inhibition was greater with carbachol or bombesin than VIP or secretin; the former secretagogues reduced the binding to 40-45%, and the latter to 75-80% of a control, respectively. These pancreatic secretagogues had no inhibitory effect on somatostatin binding when added directly to the binding media. Furthermore, the inhibitory effect of carbachol was attenuated by the presence of 1 mM EDTA in media for pretreatment, suggesting that intracellular pathways activated by pancreatic secretagogues may be responsible for somatostatin receptor modulation. Interestingly, when combined with VIP, pretreatment of acini with carbachol produced an additive inhibition of labeled somatostatin binding to the membranes. Results, therefore, suggest that somatostatin binding to its receptors in the pancreas may be regulated via two functionally distinct intracellular pathways.
研究了标记的生长抑素与胰腺腺泡膜的结合情况,以探讨胰腺促分泌素如何调节胰腺中的生长抑素受体。在37℃下用诸如卡巴胆碱和蛙皮素等胰腺促分泌素、血管活性肠肽(VIP)和促胰液素对胰腺腺泡进行120分钟预处理后,随后标记的生长抑素与腺泡膜的结合呈剂量依赖性降低。这些促分泌素对标记的生长抑素结合的抑制作用也具有时间依赖性。当腺泡与这两类促分泌素孵育超过120分钟时,它们都能最大程度地降低随后的生长抑素结合。然而,卡巴胆碱或蛙皮素的抑制程度比VIP或促胰液素更大;前两者分别将结合降低至对照的40 - 45%,而后两者降低至75 - 80%。当直接添加到结合介质中时,这些胰腺促分泌素对生长抑素结合没有抑制作用。此外,预处理介质中存在1 mM EDTA可减弱卡巴胆碱的抑制作用,这表明胰腺促分泌素激活的细胞内途径可能负责生长抑素受体的调节。有趣的是,当与VIP联合使用时,用卡巴胆碱预处理腺泡会对标记的生长抑素与膜的结合产生相加抑制作用。因此,结果表明生长抑素与其在胰腺中的受体的结合可能通过两条功能不同的细胞内途径进行调节。