Granda Michael L, Schroeder Frederick A, Borra Ronald H J, Schauer Nathan, Aisaborhale Ehimen, Guimaraes Alexander R, Hooker Jacob M
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and Eastern Virginia Medical School, Norfolk, Virginia.
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts; and.
Am J Physiol Renal Physiol. 2014 Jul 1;307(1):F116-21. doi: 10.1152/ajprenal.00111.2014. Epub 2014 May 7.
The intrarenal dopamine system is important for signaling and natriuresis, and significant dysfunction is associated with hypertension and kidney disease in ex vivo studies. Dopamine receptors also modulate and are modulated by the renin-angiotensin-aldosterone system. Here, we show the first in vivo measurement of D1-like receptors in the renal cortex of Sprague-Dawley rat and Papio anubis baboon using [(11)C]NNC 112, a positron emission tomography radioligand for D1-like receptors. In addition, we show a D1-like binding potential response to angiotensin II blockade in rats using losartan. Demonstration of self-saturable binding in the rat as well as specific and saturable binding in Papio anubis validate the use of [(11)C]NNC 112 in the first in vivo measurement of renal dopamine D1-like receptors. Furthermore, [(11)C]NNC 112 is a radioligand tool already validated for use in probing human central nervous system (CNS) D1-like receptors. Our work demonstrates specific and saturable non-CNS binding in higher animals and the ability to quantify physiological response to drug treatment and provides a clear path to extend use of [(11)C]NNC 112 to study renal dopamine in humans.
肾内多巴胺系统对信号传导和利钠作用很重要，在体外研究中，显著的功能障碍与高血压和肾脏疾病相关。多巴胺受体也调节肾素-血管紧张素-醛固酮系统，并受其调节。在此，我们首次使用[(11)C]NNC 112（一种用于D1样受体的正电子发射断层扫描放射性配体），在Sprague-Dawley大鼠和东非狒狒的肾皮质中对D1样受体进行了体内测量。此外，我们还展示了使用氯沙坦的大鼠对血管紧张素II阻断的D1样结合潜能反应。大鼠体内自饱和结合以及东非狒狒体内特异性和饱和性结合的证明，验证了[(11)C]NNC 112在首次肾多巴胺D1样受体体内测量中的应用。此外，[(11)C]NNC 112是一种已被验证可用于探测人类中枢神经系统（CNS）D1样受体的放射性配体工具。我们的研究证明了在高等动物中存在特异性和饱和性的非中枢神经系统结合，以及量化药物治疗生理反应的能力，并为将[(11)C]NNC 112扩展用于研究人类肾多巴胺提供了明确的途径。
