Endopeptidase-24.11 is the integral membrane peptidase initiating degradation of somatostatin in the hippocampus.
The membrane metalloenzyme endopeptidase-24.11 has been localized by immunocytochemistry in the porcine hippocampus in the stratum oriens and stratum radiatum. Endopeptidase-24.11 was found to be approximately 10-fold more abundant in a striatal than a hippocampal membrane preparation. Both somatostatin-28 and somatostatin-14 were metabolized by endopeptidase-24.11, but the kinetics of hydrolysis markedly favoured the smaller form of the neuropeptide. After phase separation with Triton X-114 of striatal and hippocampal membrane preparations, and by using selective inhibitors, the major (> 80%) somatostatin-metabolizing activity was found to partition into the detergent-rich phase and was attributable predominantly to endopeptidase-24.11. The residual activity observed in the presence of the selective endopeptidase-24.11 inhibitor phosphoramidon was blocked by Pro-Ile or N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate, inhibitors of endopeptidase-24.16 and endopeptidase-24.15, respectively. However, Pro-Ile, at comparable concentrations, was shown to inhibit endopeptidase-24.11, challenging the validity of its use as a selective inhibitor of endopeptidase-24.16. The immunocytochemical and Triton X-114 phase-separation data implicate endopeptidase-24.11, rather than endopeptidase-24.16 or endopeptidase-24.15, as the major physiological somatostatin-degrading neuropeptidase in the striatum and hippocampus.
Barnes
K
K
Department of Biochemistry and Molecular Biology, University of Leeds, England.
Doherty
S
S
Turner
A J
AJ
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D003902:Detergents; D004151:Dipeptides / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D006868:Hydrolysis; D007668:Kidney / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017830:Octoxynol; D011092:Polyethylene Glycols; D013004:Somatostatin / Q000378:metabolism*; D013552:Swine; D014018:Tissue Distribution
D003902:Detergents; D004151:Dipeptides; D011092:Polyethylene Glycols; D013004:Somatostatin; C092562:prolylisoleucine; D017830:Octoxynol; C010615:Nonidet P-40; D015260:Neprilysin