Kashimura J, Shimosegawa T, Mochizuki T, Yanaihara N, Koizumi M, Toyota T
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Pancreas. 1995 Mar;10(2):161-6. doi: 10.1097/00006676-199503000-00009.
Helodermin is a 35 amino acid-residue peptide of the vasoactive intestinal polypeptide (VIP) family, which was originally isolated from the venom of Heloderma suspectum on the basis of its capacity to stimulate adenylate cyclase in the rat pancreas. In the present study, using rat dispersed pancreatic acini, we examined the binding characteristics of helodermin, its action on amylase secretion, and the production of intracellular cyclic AMP (cAMP). Helodermin stimulated intracellular cAMP production dose dependently in a manner that was nearly identical to that of VIP. Helodermin stimulated amylase secretion dose dependently, showing an efficacy similar to that of VIP but with 100 times less potency than VIP. Adding 0.5 mM 3-isobutyl-1-methylxanthine increased the potency of helodermin's action on amylase secretion but did not change the efficacy. The binding study showed that the order of binding affinity to VIP receptors was VIP = helodermin > secretin, while the order of that to secretin receptors was secretin > helodermin > VIP. These results suggest that helodermin stimulated amylase secretion from rat dispersed pancreatic acini via VIP-preferring receptors that are coupled to the production of intracellular cAMP, but a part of the postreceptor mechanism for enzyme secretion is different from that of VIP.
海洛德明是一种由35个氨基酸残基组成的血管活性肠肽（VIP）家族肽，最初是从可疑希拉毒蜥的毒液中分离出来的，基于其刺激大鼠胰腺腺苷酸环化酶的能力。在本研究中，我们使用大鼠分散的胰腺腺泡，研究了海洛德明的结合特性、其对淀粉酶分泌的作用以及细胞内环磷酸腺苷（cAMP）的产生。海洛德明以与VIP几乎相同的方式剂量依赖性地刺激细胞内cAMP的产生。海洛德明剂量依赖性地刺激淀粉酶分泌，其效力与VIP相似，但效力比VIP低100倍。添加0.5 mM 3-异丁基-1-甲基黄嘌呤可增加海洛德明对淀粉酶分泌作用的效力，但不改变其效力。结合研究表明，对VIP受体的结合亲和力顺序为VIP = 海洛德明 > 促胰液素，而对促胰液素受体的结合亲和力顺序为促胰液素 > 海洛德明 > VIP。这些结果表明，海洛德明通过与细胞内cAMP产生偶联的VIP偏好受体刺激大鼠分散胰腺腺泡的淀粉酶分泌，但酶分泌的部分受体后机制与VIP不同。
