Effect of inhibitors of enkephalin degradation in the isolated guinea-pig ileum.
Bestatin and high concentration of puromycin increase the depressing effect of [Met] enkephalin on the twitch response of the electrically stimulated guinea-pig ileum. Thiorphan (enkephalinase A inhibitor) is hardly effective, but phelorphan (mercapto-acetyl-Phe-Phe) a newly synthesized enzyme-inhibitor which effectively inhibits the enkephalinase A, enkephalinase B and soluble aminopeptidase activity, potentiates the effect of enkephalin dose-dependently and in low concentrations (0.01-1 microM). Enkephalinase A, though present in these tissues, is not functional under the conditions of the test, because it is inhibited by the physiological buffer itself. These results demonstrate that enkephalinase B and the membrane bound aminopeptidase, but not the soluble aminopeptidase or enkephalinase A hydrolyse enkephalins in the isolated guinea-pig ileum.
van Amsterdam
J G
JG
Department of Pharmacy, University of Amsterdam, The Netherlands.
van Buuren
K J
KJ
Krielaart
M J
MJ
Zuiderveld
O P
OP
Tijms
R P
RP
D000818:Animals; D002021:Buffers; D004151:Dipeptides / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D015244:Thiorphan / Q000494:pharmacology*
D002021:Buffers; D004151:Dipeptides; C053652:phelorphan; D004744:Enkephalin, Methionine; D015244:Thiorphan; D015260:Neprilysin; D007930:Leucine; C012211:ubenimex