González-Yanes C, Santos-Alvarez J, Sánchez-Margalet V
Department of Medical Biochemistry and Molecular Biology, School of Medicine, University Hospital Virgen Macarena, Av. Sanchez Pizjuan 4, 41009, Seville, Spain.
Cell Signal. 2001 Jan;13(1):43-9. doi: 10.1016/s0898-6568(00)00127-3.
Pancreastatin (PST) is one of the chromogranin A (CGA)-derived peptides with known biological activity. It has a general inhibitory effect on secretion in many exocrine and endocrine systems including the heart atrium. Besides, a role of PST as a counter-regulatory peptide of insulin action has been proposed in the light of its effects on glucose and lipid metabolism in the liver and adipose tissue, where receptors and signaling have been described. Galpha(q/11) pathway seems to mediate PST action. Since PST has been shown to function as a typical calcium-dependent hormone, and increased plasma levels have been found in essential hypertension correlating with catecholamines, we sought to study its possible interaction and signaling in heart membranes. Here, we are characterizing specific PST binding sites and signaling in rat heart membranes. We have found that PST receptor has a K(d) of 0.5 nM and a B(max) of 34 fmol/mg of protein. The PST binding is inhibited by guanine nucleotides, suggesting the functional coupling of the receptor with GTP binding proteins (G proteins). Moreover, PST dose-dependently increases GTP binding to rat heart membranes. Finally, we have studied PST signaling-effector system by measuring phospholipase C (PLC) activity using blocking antibodies against different G proteins and PLC isoforms. We have found that PST stimulates PLCbeta(2)>PLCbeta(1)>PLCbeta(3) by activating Galpha(16) in rat heart membranes. These data suggest that PST may modulate the cardiac function.
胰抑制素（PST）是一种具有已知生物活性的嗜铬粒蛋白A（CGA）衍生肽。它对包括心房在内的许多外分泌和内分泌系统的分泌具有普遍抑制作用。此外，鉴于其对肝脏和脂肪组织中葡萄糖和脂质代谢的影响，有人提出PST作为胰岛素作用的反调节肽，其中已描述了受体和信号传导。Gα（q/11）途径似乎介导PST的作用。由于PST已被证明作为一种典型的钙依赖性激素发挥作用，并且在原发性高血压患者中发现血浆水平升高与儿茶酚胺相关，我们试图研究其在心脏膜中的可能相互作用和信号传导。在这里，我们正在表征大鼠心脏膜中特定的PST结合位点和信号传导。我们发现PST受体的解离常数（K(d)）为0.5 nM，最大结合容量（B(max)）为34 fmol/mg蛋白质。PST结合受到鸟嘌呤核苷酸的抑制，表明受体与GTP结合蛋白（G蛋白）存在功能偶联。此外，PST剂量依赖性地增加GTP与大鼠心脏膜的结合。最后，我们通过使用针对不同G蛋白和PLC亚型的阻断抗体测量磷脂酶C（PLC）活性来研究PST信号效应系统。我们发现PST通过激活大鼠心脏膜中的Gα(16)刺激PLCβ(2)>PLCβ(1)>PLCβ(3)。这些数据表明PST可能调节心脏功能。
