Chang C H, Chey W Y, Erway B, Coy D H, Chang T M
The Konar Center for Digestive and Liver Diseases, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Am J Physiol. 1998 Aug;275(2):G192-202. doi: 10.1152/ajpgi.1998.275.2.G192.
Nerve fibers containing bombesin (BB)/gastrin-releasing polypeptide (GRP), pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP), or galanin are known to innervate the mucosa of the upper small intestine. Both BB/GRP and PACAP have been shown to elicit secretin secretion in vivo. We studied whether the above-mentioned neuropeptides can act directly on secretin-producing cells, including the murine neuroendocrine cell line STC-1 and a secretin cell-enriched preparation isolated from rat upper small intestinal mucosa. Secretin release from both cell types was stimulated by various agents known to elicit secretin release and by the neuropeptides BB, GRP, and PACAP, suggesting a comparable response between the two cell preparations. The effects of neuropeptides were further studied in STC-1 cells. BB, GRP, and PACAP stimulated secretin release time and concentration dependently. VIP also stimulated secretin release concentration dependently. Stimulation by BB/GRP or PACAP was accompanied by elevation of inositol-1,4,5-trisphosphate (IP3) or cAMP, respectively. The stimulatory effect of PACAP on secretin release was synergistically enhanced by BB without any synergistic increase in IP3 or cAMP production, suggesting cross talk between different signal transduction pathways downstream of the production of these two second messengers. The L-type Ca2+ channel blocker diltiazem (10 microM) and the Ca2+ chelator EGTA (1 mM) significantly inhibited BB-stimulated secretin release by 64% and 59%, respectively, and inhibited PACAP-stimulated release by 75% and 55%, respectively. The protein kinase A-specific inhibitor Rp-cAMPS (100 microM) also inhibited both BB- and PACAP-stimulated secretin release by 30% and 62%, respectively. Galanin inhibited BB- and PACAP-stimulated secretin release and production of second messengers in a concentration-dependent and pertussis toxin-sensitive manner. These results suggested that the neuropeptides BB/GRP, PACAP, VIP, and galanin can modulate secretin release in secretin-producing cells and that STC-1 cells can serve as a useful model for studying the cellular mechanism of secretin secretion elicited by luminal secretagogues and neuropeptides.
已知含有蛙皮素（BB）/胃泌素释放肽（GRP）、垂体腺苷酸环化酶激活肽（PACAP）、血管活性肠肽（VIP）或甘丙肽的神经纤维支配上小肠黏膜。BB/GRP和PACAP在体内均已被证明能引发促胰液素分泌。我们研究了上述神经肽是否能直接作用于促胰液素分泌细胞，包括小鼠神经内分泌细胞系STC - 1和从大鼠上小肠黏膜分离的富含促胰液素细胞的制剂。已知能引发促胰液素释放的各种试剂以及神经肽BB、GRP和PACAP均刺激了这两种细胞类型的促胰液素释放，表明两种细胞制剂之间有类似的反应。在STC - 1细胞中进一步研究了神经肽的作用。BB、GRP和PACAP刺激促胰液素释放具有时间和浓度依赖性。VIP也以浓度依赖性方式刺激促胰液素释放。BB/GRP或PACAP的刺激分别伴随着肌醇 - 1,4,5 - 三磷酸（IP3）或环磷酸腺苷（cAMP）的升高。PACAP对促胰液素释放的刺激作用被BB协同增强，而IP3或cAMP的产生没有任何协同增加，这表明在这两种第二信使产生下游的不同信号转导途径之间存在相互作用。L型钙通道阻滞剂地尔硫䓬（10微摩尔）和钙螯合剂乙二醇双四乙酸（EGTA，1毫摩尔）分别显著抑制BB刺激的促胰液素释放64%和59%，并分别抑制PACAP刺激的释放75%和55%。蛋白激酶A特异性抑制剂Rp - cAMPS（100微摩尔）也分别抑制BB和PACAP刺激的促胰液素释放30%和62%。甘丙肽以浓度依赖性和百日咳毒素敏感的方式抑制BB和PACAP刺激的促胰液素释放以及第二信使的产生。这些结果表明，神经肽BB/GRP、PACAP、VIP和甘丙肽可以调节促胰液素分泌细胞中的促胰液素释放，并且STC - 1细胞可作为研究腔内促分泌素和神经肽引发促胰液素分泌的细胞机制的有用模型。
