Inhibition of the enzymatic degradation of leu-enkephalin by puromycin

Effects of Peptidase Inhibitors on the (Met5)-Enkephalin Hydrolysis in Ileal and Striatal Preparations of Guinea-Pig: Almost Complete Protection of Degradation by the Combination of Amastatin, Captopril and Thiorphan

“…Additionally, the fact that puromycin has a quite low ability to inhibit the enkephalin hydrolyzing aminopeptidase in an ileal mem brane fraction supports the previous finding (1, 7) that the inhibitory potency of enkephalin in guinea-pig ileum is not enhanced by puromycin, since the mem brane-bound aminopeptidase must be more correlated than the soluble one to the potency of the exogenously given enkephalin (1). Moreover, the finding that puromycin has a significant inhibitory action on the enkephalin hydrolyzing aminopeptidase in striatal pre parations is consistent with the result reported previously (8). It is noteworthy that the difference exists between the enkephalin hydrolyzing aminopeptidase in a striatal membrane fraction and that in an ileal membrane fraction in terms of the sensitivity to puromycin, since the membrane-bound aminopeptidase must be more important than the soluble one to terminate the action of both the enkephalin released from the presynaptic nerve terminal and that added exogenously.…”

In vitro Human Plasma Leucine⁵-Enkephalin Degradation Is Inhibited by a Select Number of Drugs with the Phenothiazine Molecule in Their Chemical Structure

“…Anecdotal reports suggest that endogenous 'as yet-unidentified, possible of peptidic nature, circulating substances' [28,35,36], play a significant role in regulating plasmatic LEU degradation rate, and therefore its circulating plasma levels. It has been claimed that a number of clinically used drugs, showing widely different molecular structure and biological activity have a significant effect, mostly inhibitory on in vitro plasmatic or tissue enkephalin metabolism e.g., some antibiotics, neuroleptics, antidepressants, narcotic analgesics and barbiturates [18][19][20][21][22][23][24]. However, a number of other equally diverse substances e.g., various monoamine neurotransmitters, substances of abuse, nonsteroidal an-tiinflammatory agents and miscellaneous compounds, do not appear to significantly alter plasmatic LEU degradation kinetics [13].…”

“…Thus, reports that a number of endogenous chemicals, including some monoamine neurotransmitters, as well as some representatives from various currently used classes of drugs showing widely different chemical structure e.g., antibiotics, neuroleptics, tricyclic antidepressants, narcotic analgesics, and barbiturates may significantly affect plasmatic aminopeptidase activity [18][19][20][21][22][23][24], raised the possibility of using these or similar agents to better understand the possible role of LEU in health and disease states.…”

The Role of Bestatin-Sensitive Aminopeptidase, Angiotensin Converting Enzyme and Thiorphan-Sensitive "Enkephalinase" in the Potency of Enkephalins in the Guinea-Pig Ileum

“…However, controversy exists over the augmentative effectiveness of peptidase in hibitors against the inhibitory potency of enkephalin in guinea-pig ileum. The anti biotic puromycin, which had been shown to be an effective inhibitor of the hydrolysis of enkephalin by brain homogenate (6), was reported to prolong greatly the depressant effect of enkephalin on the electrically induced contractions of guinea-pig ileum (1). However, Cohen et al (2) showed that the inhibitory potency of enkephalin in guinea-pig ileum was not enhanced by puromycin, but augmented by bestatin, an aminopeptidase inhibitor of bacterial origin (7); and the degradation of 3H-enkephalin after incubation with guinea-pig ileum was not altered with puromycin, but decreased with bestatin.…”