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, 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.
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.
M D
MD
Perloff
R M
RM
Kream
M C
MC
Beinfeld
D000818:Animals; D001921:Brain / Q000378:metabolism*; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D011863:Radioimmunoassay; D051381:Rats; D013373:Substance P / Q000378:metabolism*
D013373:Substance P; D002268:Carboxypeptidases; D043423:Carboxypeptidase H