Neuropeptide-hydrolysing activities in synaptosomal fractions from dog ileum myenteric, deep muscular and submucous plexi. Their participation in neurotensin inactivation.
The mapping of neuropeptidases in synaptosomal fractions prepared from dog ileum myenteric, deep muscular and submucous plexus was established by means of fluorigenic substrates and specific inhibitors. Endopeptidase 24.11, angiotensin-converting enzyme and aminopeptidases were found in all tissues, the highest amounts being recovered in the submucous preparation. Post-proline dipeptidyl aminopeptidase was obtained in high quantities whatever the tissue source while proline endopeptidase was detected in low amounts and pyroglutamyl-peptide hydrolase was never detectable. The above peptidases were examined for their putative participation in the inactivation of neurotensin by monitoring the effect of specific inhibitors on the formation of the metabolites of labeled neurotensin separated by HPLC. Endopeptidases 24.11, 24.15 and 24.16 were respectively responsible for the formation of neurotensin(1-11), neurotensin(1-8) and neurotensin(1-10) that are devoid of biological activity. The secondary attacks occurring on neurotensin degradation products were the following: cleavage of neurotensin(1-10) into neurotensin(1-8) by angiotensin-converting enzyme; conversion of neurotensin(9-13) into neurotensin(11-13) by post-proline dipeptidyl aminopeptidase; hydrolysis of neurotensin(11-13) into free tyrosine by aminopeptidase(s).
Barelli
H
H
Centre National de la Recherche Scientifique, Faculté des Sciences, Nice, France.
Ahmad
S
S
Kostka
P
P
Fox
J A
JA
Daniel
E E
EE
Vincent
J P
JP
Checler
F
F
D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D010450:Endopeptidases / Q000378:metabolism; D005470:Fluorometry; D006868:Hydrolysis; D007082:Ileum / Q000294:innervation*; D008566:Membranes / Q000201:enzymology; D008666:Metalloendopeptidases / Q000378:metabolism; D009197:Myenteric Plexus / Q000201:enzymology*; D015260:Neprilysin / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D000085822:Prolyl Oligopeptidases; D011751:Pyroglutamyl-Peptidase I / Q000378:metabolism; D012697:Serine Endopeptidases; D013368:Submucous Plexus / Q000201:enzymology*; D013574:Synaptosomes / Q000201:enzymology*
D009479:Neuropeptides; D009496:Neurotensin; D010450:Endopeptidases; D000626:Aminopeptidases; D007703:Peptidyl-Dipeptidase A; D011751:Pyroglutamyl-Peptidase I; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; C022510:thimet oligopeptidase; C062316:neurolysin