Metabolic half-life of somatostatin and peptidase activities are altered in Alzheimer's disease.
Several reports have described decreased immunoreactive somatostatin levels in specific regions of post-mortem brain tissue from patients diagnosed with senile dementia of the Alzheimer type (SDAT). In an attempt to determine if the metabolism of somatostatin is also altered as a result of SDAT, we examined the regional metabolic half-life of somatostatin-28 (SS-28) and somatostatin-14 (SS-14). The activity of the following peptidases was also determined: neutral endopeptidase E.C. 3.4.24.11; metalloendopeptidase E.C. 3.4.24.15; carboxypeptidase E (E.C. 3.4.17.10); and trypsin-like serine protease. The metabolic half-life of SS-28 was significantly reduced in post-mortem Brodmann Area 22 of SDAT tissue. This decrease in SS-28 metabolic half-life was correlated with a significant increase in trypsin-like serine protease activity in the same SDAT brain region. The formation rate of SS-14 from SS-28 incubated with Brodmann Area 22 homogenates was also increased in SDAT tissues as compared to controls. A regional variation in neutral endopeptidase E.C. 3.4.24.11 was also noted in both controls and SDAT samples. Although postmortem intervals of samples varied significantly, no effect was seen on any biochemical parameter measured. Results from this study provide evidence that a correlation can be made between changes in metabolic half-life somatostatin and alterations in neuropeptidase activities due to SDAT. As these data show alterations in both proteolytic metabolism and peptidase activities, many other biologically active peptide substrates could also be affected in SDAT.
Weber
S J
SJ
Department of Pharmacology, University of Arizona College of Medicine.
Louis
R B
RB
Trombley
L
L
Bissette
G
G
Davies
P
P
Davis
T P
TP
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D008666:Metalloendopeptidases / Q000378:metabolism; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D011180:Postmortem Changes; D012697:Serine Endopeptidases / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism*; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism
D013004:Somatostatin; D002268:Carboxypeptidases; D010450:Endopeptidases; D043423:Carboxypeptidase H; D012697:Serine Endopeptidases; D014357:Trypsin; D008666:Metalloendopeptidases; D015260:Neprilysin