Perloff M D, Kream R M, Beinfeld M C
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
Peptides. 1998;19(6):1115-7. doi: 10.1016/s0196-9781(98)00010-2.
This study examines the role of carboxypeptidase E (CPE) in processing pro tachykinin to form the final bioactive amidated undecapeptide, substance P (SP) in various rat brain regions. Cpe(fat)/Cpe(fat) mice brain tissue was analyzed for total SP forms (including intermediates), and final amidated SP was compared to Cpe+/Cpe+ and Cpe+/Cpe- controls. In all brain regions tested by radioimmunoassay, amidated fully processed SP was more than fivefold lower in Cpe(fat)/Cpe(fat) mice than in controls whereas total SP species levels were unchanged. This demonstrates that CPE is required for normal SP proteolytic processing. Substance P has numerous functions in the brain; therefore, SP deficiency due to the CPE mutation may contribute to the obese phenotype or even to other phenotypes not yet described in Cpe(fat)/Cpe(fat) mice.
本研究考察了羧肽酶E（CPE）在将前速激肽加工成最终具有生物活性的酰胺化十一肽P物质（SP）过程中在大鼠不同脑区所起的作用。对Cpe(fat)/Cpe(fat)小鼠脑组织中的总SP形式（包括中间产物）进行分析，并将最终的酰胺化SP与Cpe+/Cpe+和Cpe+/Cpe-对照进行比较。在通过放射免疫测定法检测的所有脑区中，Cpe(fat)/Cpe(fat)小鼠体内酰胺化完全加工的SP比对照低五倍以上，而总SP种类水平未变。这表明正常的SP蛋白水解加工需要CPE。P物质在大脑中有多种功能；因此，由于CPE突变导致的SP缺乏可能导致肥胖表型，甚至可能导致Cpe(fat)/Cpe(fat)小鼠尚未描述的其他表型。
