Zdon M J, Adrian T E, Modlin I M
Gastrointestinal Surgical Research Group, Yale University School of Medicine, West Haven, Connecticut.
J Surg Res. 1988 Jun;44(6):680-6. doi: 10.1016/0022-4804(88)90100-x.
It has previously been demonstrated that somatostatin (SRIF) directly inhibits parietal cell secretion. However, the significance of SRIF as a paracrine agent and mechanisms of local gastric SRIF release are not clear. Vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) are neuropeptides which have been localized in the gastric fundus and have been demonstrated to inhibit gastric acid secretion in vivo. The present study examines the hypothesis that CGRP and VIP act via the release of gastric fundic SRIF. The study utilized rabbit isolated gastric glands prepared by collagenase digestion. Glands were incubated alone, or with 10(-10)-10(-6) M CGRP or 10(-10)-10(-6) M VIP for 30 min. Supernatant SRIF was measured using a specific radioimmunoassay. Unstimulated SRIF release was 101 +/- 16 fmole/ml. CGRP (10(-7) and 10(-6) M) and VIP (10(-7) and 10(-6) M) resulted in significant SRIF release. The maximum release of SRIF by CGRP (506 +/- 113 fmole/ml) was significantly greater than that by VIP (293 +/- 33 fmole/ml) (P less than 0.05). However, both these concentrations of SRIF are comparable to the ID50 concentration (4.5 X 10(-10) M) for SRIF inhibition of acid secretion by isolated parietal cells as assessed by [14C]aminopyrine accumulation. These results are consistent with the hypothesis that CGRP and VIP inhibition of acid secretion may be mediated, at least in part, by the local release of SRIF from the gastric fundus. These data further support the significance of paracrine interactions in the modulation of cellular secretory function.
先前已有研究表明，生长抑素（SRIF）可直接抑制壁细胞分泌。然而，SRIF作为旁分泌因子的意义以及胃局部SRIF释放的机制尚不清楚。血管活性肠肽（VIP）和降钙素基因相关肽（CGRP）是神经肽，已定位在胃底，且已证实在体内可抑制胃酸分泌。本研究检验了CGRP和VIP通过释放胃底SRIF发挥作用的假说。该研究使用了经胶原酶消化制备的兔离体胃腺。胃腺单独孵育，或与10（-10）-10（-6）M CGRP或10（-10）-10（-6）M VIP孵育30分钟。使用特异性放射免疫测定法测量上清液中的SRIF。未刺激时SRIF释放量为101±16飞摩尔/毫升。CGRP（10（-7）和10（-6）M）和VIP（10（-7）和10（-6）M）导致SRIF显著释放。CGRP引起的SRIF最大释放量（506±113飞摩尔/毫升）显著高于VIP（293±33飞摩尔/毫升）（P＜0.05）。然而，这两种浓度的SRIF均与通过[14C]氨基比林积累评估的SRIF抑制离体壁细胞酸分泌的半数抑制浓度（ID50浓度，4.5×10（-10）M）相当。这些结果与CGRP和VIP抑制酸分泌可能至少部分由胃底局部释放SRIF介导的假说一致。这些数据进一步支持了旁分泌相互作用在调节细胞分泌功能中的重要性。
