垂体腺苷酸环化酶激活肽（PACAP）和血管活性肠肽（VIP）通过与VIP/PACAP-2受体相互作用刺激大鼠胰腺腺泡中的酶分泌：对胆囊收缩素/卡巴胆碱诱导的酶释放有相加增强作用。

PACAP and VIP stimulate enzyme secretion in rat pancreatic acini via interaction with VIP/PACAP-2 receptors: additive augmentation of CCK/carbachol-induced enzyme release.

作者信息

Schmidt W E, Seebeck J, Höcker M, Schwarzhoff R, Schäfer H, Fornefeld H, Morys-Wortmann C, Fölsch U R, Creutzfeldt W

机构信息

Department of Medicine, Georg August University of Göttingen, Germany.

出版信息

Pancreas. 1993 Jul;8(4):476-87. doi: 10.1097/00006676-199307000-00012.

DOI:10.1097/00006676-199307000-00012

PMID:8103217

Abstract

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 microM), PACAP(1-23) (8.2 +/- 1.5 microM), VIP (> 30 microM), PACAP(3-27), PACAP(1-19), PACAP(3-19), PACAP(1-12), and PACAP(18-38) (all > 50 microM) 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 "VIP/PACAP-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 VIP/PACAP-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-24-28), 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 VIP/PACAP-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.

摘要

垂体腺苷酸环化酶激活多肽（PACAP）是一种与血管活性肠肽（VIP）具有高度序列同源性的新型下丘脑肽，我们在大鼠AR 4-2 J胰腺癌细胞和分离的大鼠胰腺腺泡中研究了其结合特性和生物学效应。PACAP(1 - 27)和类似物PACAP(1 - 23, VIP - 24 - 28)，而非VIP，能有效且可逆地将125I - PACAP(1 - 27)从与AR 4-2 J细胞上大量表达的高亲和力PACAP优先受体（称为“PACAP - 1受体”）的结合中置换出来。高亲和力结合依赖于PACAP(1 - 27)的N端和C端残基：PACAP(1 - 24,Cys - 25)（7.3±1.6 microM）、PACAP(1 - 23)（8.2±1.5 microM）、VIP（>30 microM）、PACAP(3 - 27)、PACAP(1 - 19)、PACAP(3 - 19)、PACAP(1 - 12)和PACAP(18 - 38)（均>50 microM）显示出低结合力或无结合力。相比之下，PACAP(1 - 27)和VIP能等效力地置换125I - VIP与AR 4-2 J细胞的高亲和力和低亲和力结合，因此在这些细胞上还定义了两个几乎不表达的结合位点，称为“VIP/PACAP - 2受体”，与先前描述的高亲和力和低亲和力腺泡VIP受体相似或相同。125I - PACAP(1 - 27)与大鼠胰腺腺泡上的高亲和力和低亲和力结合位点的结合被PACAP(1 - 27)和VIP等效力抑制，将这些位点鉴定为VIP/PACAP - 2受体。PACAP(1 - 23)识别两种类型的结合位点，亲和力仅略低。PACAP(1 - 27)、PACAP(1 - 38)、PACAP(1 - 23, VIP - 24 - 28)和PACAP(1 - 23)能等效力地刺激胰腺腺泡中的脂肪酶释放和环磷酸腺苷生成。PACAP(1 - 27)或VIP与胆囊收缩素 - 8或卡巴胆碱共同孵育显示对酶分泌有相加作用。我们的结果表明，VIP/PACAP - 2受体在大鼠胰腺腺泡上占主导表达，而AR 4-2 J细胞主要表达PACAP - 1受体。PACAP是两种受体类型的有效配体，必须被视为一种新型的类VIP胰腺促分泌素。