Whitcomb D C, Vigna S R, McVey D C, Taylor I L
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Am J Physiol. 1992 Mar;262(3 Pt 1):G532-6. doi: 10.1152/ajpgi.1992.262.3.G532.
Pancreatic polypeptide (PP) is released from pancreatic islets after meals or in response to stress. Although PP exhibits a wide spectrum of biological effects, few, if any, are mediated by a direct action of PP on its ultimate target organ. Recently, PP receptors have been identified in areas of the brain with an incomplete blood-brain barrier suggesting that PP may act indirectly through the central nervous system. In the present study, we sought to identify peripheral PP binding sites using an in vivo radioreceptor assay and in vitro autoradiography. Using these techniques, we have identified saturable binding sites for PP in the zona fasciculata, zona reticularis, and the medulla of the rat adrenal gland. We have characterized these sites using equilibrium analysis of membrane-radioligand binding and by quantitative autoradiography of radioligand binding to frozen tissue sections. Binding of PP to these sites is saturable, of high affinity, and specific as well as time, temperature, and membrane dependent. Moreover, PP binds to these putative receptor sites in vivo at physiological concentrations. Many of the actions of PPs have been demonstrated to be indirect. Because PP receptors have been identified in the brain and now in the adrenal gland, we suggest that some of the effects of PP may be mediated through direct and indirect modulation of the brain and adrenal axis.
餐后或应激时,胰岛会释放胰多肽(PP)。尽管PP具有广泛的生物学效应,但即便有,也很少是通过PP对其最终靶器官的直接作用介导的。最近,在血脑屏障不完整的脑区已鉴定出PP受体,这表明PP可能通过中枢神经系统间接发挥作用。在本研究中,我们试图使用体内放射受体分析法和体外放射自显影法来鉴定外周PP结合位点。利用这些技术,我们在大鼠肾上腺的束状带、网状带和髓质中鉴定出了PP的可饱和结合位点。我们通过膜-放射性配体结合的平衡分析以及放射性配体与冷冻组织切片结合的定量放射自显影来表征这些位点。PP与这些位点的结合是可饱和的、具有高亲和力且具有特异性,同时还依赖时间、温度和膜。此外,PP在生理浓度下可在体内与这些假定的受体位点结合。已证明PP的许多作用是间接的。由于已在脑以及现在在肾上腺中鉴定出PP受体,我们认为PP的某些作用可能是通过对脑和肾上腺轴的直接和间接调节介导的。