Differential processing of substance P and neurokinin A by plasma dipeptidyl(amino)peptidase IV, aminopeptidase M and angiotensin converting enzyme.
In addition to plasma metabolism of substance P (SP) by angiotensin converting enzyme (ACE; EC 3.4.15.1) (less than 1.0 nmol/min/ml), the majority of SP hydrolysis by rat and human plasma was due to dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) (3.15-5.91 nmol/min/ml), which sequentially converted SP to SP(3-11) and SP(5-11). In turn, the SP(5-11) metabolite was rapidly hydrolyzed by rat and human plasma aminopeptidase M (AmM; EC 3.4.11.2) (24.2-25.5 nmol/min/ml). The Km values of SP for DAP IV and of SP(5-11) for AmM ranged from 32.7 to 123 microM. In contrast, neurokinin A (NKA) was resistant to both ACE and DAP IV but was subject to N-terminal hydrolysis by AmM (3.76-10.8 nmol/min/ml; Km = 90.7 microM). These data demonstrate differential processing of SP and NKA by specific peptidases in rat and human plasma.
Wang
L H
LH
Department of Physiology, Ohio State University, Columbus 43210.
Ahmad
S
S
Benter
I F
IF
Chow
A
A
Mizutani
S
S
Ward
P E
PE
D000626:Aminopeptidases / Q000097:blood; D000818:Animals; D000900:Anti-Bacterial Agents; D018826:CD13 Antigens; D002216:Captopril / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D015288:Neurokinin A / Q000097:blood*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D051381:Rats; D013045:Species Specificity; D013373:Substance P / Q000097:blood*
D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D013373:Substance P; C016977:amastatin; D015288:Neurokinin A; C041445:diprotin A; D002216:Captopril; D000626:Aminopeptidases; D018826:CD13 Antigens; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; D007703:Peptidyl-Dipeptidase A