REDUCED LEVELS OF SUBSTANCE-P IN THE BRAINS OF CPE(FAT) CPE(FAT) MICE/

This study examines the role of carboxypeptidase E (CPE) in processing pro tachykinin to form the final bioactive amidated undecapeptide, su bstance P (SP) in various rat brain regions. Cpe(fat)/Cpe(fat) mice br ain 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 fu lly processed SP was more than fivefold lower in Cpe(fat)/Cpe(fat) mic e than in controls whereas total SP species levels were unchanged. Thi s demonstrates that CPE is required for normal SP proteolycic processi ng. Substance P has numerous functions in the brain therefore, SP defi ciency due to the CPE mutation may contribute to the obese phenotype o r even to other phenotypes not yet described in Cpefat/Cpe(fat) mice. (C) 1998 Elsevier Science Inc.