PACAP and VIP Stimulate Enzyme Secretion in Rat Pancreatic Acini via Interaction with VIPIPACAP‐2 Receptors: Additive Augmentation of CCK/Carbachol‐Induced Enzyme Release
PACAP and VIP Stimulate Enzyme Secretion in Rat Pancreatic Acini via Interaction with VIPIPACAP‐2 Receptors: Additive Augmentation of CCK/Carbachol‐Induced Enzyme Release
复制标题
PACAP 和 VIP 通过与 VIPIPACAP-2 受体相互作用刺激大鼠胰腺腺泡的酶分泌：CCK/卡巴胆碱诱导的酶释放的附加增强
作者：
W. Schmidt;J. Seebeck;M. Höcker;R. Schwarzhoff;H. Schäfer;Heike Fornefeld;C. Morys;U. Fölsch;W. Creutzfeldt
研究了一种与血管活性肠肽(VIP)高度同源的新的下丘脑多肽--垂体腺苷环化酶激活多肽(PACAP)对大鼠胰腺癌细胞AR 4-2 J和大鼠胰腺腺泡细胞的结合作用及其生物学效应。PACAP(1-27)和类似物PACAP(1-23，VIP-24-28)，但不是VIP，能有效且可逆地取代125I-PACAP(1-27)，使其与AR 4-2 J细胞上高亲和力的PACAP受体结合，称为“PACAP-1受体”。高亲和力结合依赖于PACAP(1-27)的N-末端和C-末端残基：PACAP(1-24，Cys-25)(7.3±1.6PIM)，PACAP(1-23)(8.2±1.5μM)，VIP(&gT；30μM)，PACAP(3-27)，PACAP(1-19)，PACAP(3-19)，PACAP(1-12)和PACAP(18-38)(ALL>；50μM)显示低结合或无结合。相反，125I-VIP与AR 4-2 J细胞的高亲和力和低亲和力结合被PACAP(1-27)和VIP等量取代，从而在这些细胞上定义了两个几乎不表达的结合部位，命名为“VIPACAP-2受体”，类似于或相同于先前描述的高亲和力和低亲和力的腺泡VIP受体。PACAP(1-27)和VIP可有效地抑制125I PACAP(1-27)与大鼠胰腺腺泡上高、低亲和力结合部位的结合，确认这些部位为VIPPACAP-2受体。PACAP(1-23)识别这两个2型结合位点，但亲和力略低。PACAP(1-27)、PACAP(1-38)、PACAP(1-23，VIP-2428)和PACAP(1-23)对腺泡脂肪酶的释放和环磷酸腺苷的生成具有同等的促进作用。PACAP(1-27)或VIP与CCK-8或卡巴胆碱共同孵育对酶的分泌有相加作用。结果提示，VIPPACAP-2受体主要表达于大鼠胰腺腺泡内，而AR 4-2J细胞主要表达PACAP-1受体。PACAP是这两种受体的有效配体，被认为是一种新的VIP样胰腺促分泌剂。
The binding and biological effect of pituitary adenylate cyclase activating polypeptide (PACAP), a novel hypothalamic peptide with high sequence homology to vasoactive intestinal polypeptide (VIP), were studied in rat AR 4–2 J pancreatic carcinoma cells and isolated rat pancreatic acini. PACAP(1–27) and analogue PACAP(1–23, VIP-24-28), but not VIP, displaced potently and reversibly 125I-PACAP(1–27) from binding to an abundantly expressed high affinity PACAP-preferring receptor on AR 4–2 J cells, referred to as “PACAP-1 receptor.” High affinity binding was dependent on N-terminal and C-terminal residues of PACAP(1–27): PACAP(1–24,Cys-25) (7.3 ± 1.6 PIM), PACAP(1–23) (8.2 ± 1.5 μM), VIP (>30 μM), PACAP(3–27), PACAP(1–19), PACAP(3–19), PACAP(1–12), and PACAP(18–38) (all >50 μM) showed low or no binding potency. In contrast, high and low affinity binding of 125I-VIP to AR 4–2 J cells was displaced equipotently by PACAP(1–27) and VIP, thus defining on these cells, in addition, two scarcely expressed binding sites, designated “VIPIPACAP-2 receptor,” similar or identical to the previously described high and low affinity acinar VIP receptor. Binding of 125I PACAP(1–27) to a high and low affinity binding site on rat pancreatic acini was inhibited equipotently by PACAP(1–27) and VIP, identifying these sites as VIPPACAP-2 receptors. PACAP(1–23) recognized both type 2 binding sites with only slightly lower affinity. PACAP(1–27), PACAP(1–38), PACAP(1–23,VIP-2428), and PACAP(1–23) equipotently stimulated acinar lipase release and cyclic AMP production in pancreatic acini. Co-incubation of PACAP(1–27) or VIP with cholecystokinin-8 or carbachol revealed additive effects on enzyme secretion. Our results suggest the predominant expression of VIPPACAP-2 receptors on rat pancreatic acini, whereas AR 4–2 J cells express mainly PACAP-1 receptors. PACAP is a potent ligand for both receptor types and has to be regarded as a novel VIP-like pancreatic secretagogue.
大鼠星形胶质细胞中垂体腺苷酸环化酶激活多肽 (PACAP) 的特异性结合位点的演示。
DOI：
10.1016/0006-291x(90)91132-c
发表时间：
1990
影响因子：
3.1
作者：
Tatsuno,I;Gottschall,PE;Köves,K;Arimura,A
通讯作者：
Arimura,A
大鼠肝膜中的 PACAP 和 VIP 受体。
DOI：
10.1152/ajpgi.1991.260.1.g97
发表时间：
1991
期刊：
The American journal of physiology
影响因子：
--
作者：
Robberecht,P;Gourlet,P;Cauvin,A;Buscail,L;DeNeef,P;Arimura,A;Christophe,J
通讯作者：
Christophe,J
DOI：
10.1016/0006-291x(90)92140-u
发表时间：
1990-07-31
影响因子：
3.1
作者：
MIYATA, A;JIANG, L;ARIMURA, A
通讯作者：
ARIMURA, A