PACAP and PACAP receptors in insulin producing tissues: localization and effects
PACAP and PACAP receptors in insulin producing tissues: localization and effects
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DOI：
10.1016/s0167-0115(98)00037-8
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发表时间：
1998-06-30
影响因子：
--
通讯作者：
Ahren, B
中科院分区：
文献类型：
--
作者：
Filipsson, K;Sundler, F;Ahren, B
我们研究了神经肽垂体腺苷酸环化酶激活多肽（PACAP）在胰岛素分泌组织中的定位、受体占有率和效力。免疫细胞化学显示PACAP样免疫反应（PACAP-IR）定位于胰腺神经，在小鼠和大鼠的胰内神经节中积聚。与此相反，PACAP-IR不能证明在内分泌细胞。此外，原位杂交，使用寡脱氧核苷酸探针识别mRNA的PACAP受体，表明小鼠和大鼠胰腺，和胰岛素瘤细胞系HIT-T15和RINm 5 F，表达PACAP 1型和VIP 2/PACAP受体。此外，PACAP 27和PACAP 38都以剂量依赖性（0.1 nM至100 nM）和等效性刺激分离的小鼠和大鼠胰岛以及HIT-T15和RINm 5 F细胞中的胰岛素分泌。此外，在小鼠胰岛中，血管活性肠多肽（VIP）在刺激胰岛素分泌方面与PACAP具有相同的效力。在小鼠中，PACAP也在1 fM的低剂量下刺激分离的胰岛的亚部分中的胰岛素分泌。因此，（1）PACAP是胰腺中唯一的神经肽，（2）胰岛素产生细胞表达PACAP 1型和VIP 2/PACAP受体，（3）两种形式的PACAP同等地刺激胰岛素分泌。基于这些结果，我们认为PACAP参与了胰岛素分泌的神经调节。(C)1998年Elsevier Science B.V.
We have studied the localization, receptor occupancy and potency of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in insulin-producing tissues. Immunocytochemistry showed that PACAP-like immunoreactivity (PACAP-IR) was localized to pancreatic nerves with accumulation in intrapancreatic ganglia in both mouse and rat. In contrast, PACAP-IR could not be demonstrated in endocrine cells. Furthermore, in situ hybridization, using oligodeoxyribonucleotide probes recognizing mRNA for PACAP receptors, demonstrated that mouse and rat pancreas, and the insulinoma cell lines HIT-T15 and RINm5F, expressed both the PACAP type 1 and the VIP2/PACAP receptors. Moreover, both PACAP27 and PACAP38 dose-dependently (0.1 nM to 100 nM) and equipotently stimulated insulin secretion in isolated mouse and rat islets and in HIT-T15 and RINm5F cells. Furthermore, in mouse islets, vasoactive intestinal polypeptide (VIP) was of equal potency as PACAP at stimulating insulin secretion. In mouse, PACAP also stimulated insulin secretion in a subfraction of the isolated islets also at the low dose of 1 fM. Thus, (1) PACAP is exclusively a neuropeptide in the pancreas, (2) insulin-producing cells express PACAP type 1 and VIP2/PACAP receptors and (3) the two forms of PACAP equipotently stimulate insulin secretion. Based on these results, we suggest that PACAP is involved in the neural regulation of insulin secretion. (C) 1998 Elsevier Science B.V.