N-terminal degradation of low molecular weight opioid peptides in human cerebrospinal fluid

Benter, İbrahim F.; Hirsh, Eva M.; Tuchmani, Alan J.; Ward, Patrick E.

doi:10.1016/0006-2952(90)90544-u

Cited by 22 publications

(13 citation statements)

References 34 publications

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“…It is not known at present, however, whether or not the hydrolysis of dyn-(1-8) in the cerebrospinal fluid (CSF) is also completely prevented by the three PIs. Low molecular weight opioid peptides such as met-enk, dyn-(1-7) and dyn-(1-10) are shown to be hydrolyzed in CSF mainly by aminopeptidase M that is inhibited by amastatin, and the other peptidase activities are suggested to be low in CSF (Benter et al 1990). Two reports (Benter et al 1990;Hiranuma et al 1998) indicate that the hydrolysis of dyn-(1-8) administered i.t.v.…”

Section: Discussionmentioning

confidence: 94%

Effects of peptidase inhibitors on anti-nociceptive action of dynorphin-(1–8) in rats

Kitamura

Akahori

Yano

et al. 2000

Naunyn-Schmiedeberg's Arch Pharmacol

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Previous in vitro studies showed that the degradation of dynorphin-(1-8) [dyn-(1-8)] by cerebral membrane preparations is almost completely prevented by a mixture of three peptidase inhibitors (PIs), amastatin, captopril and phosphoramidon. In the present investigations, effects of the three PIs on the anti-nociception induced by the intra-third-ventricular (i.t.v.) administration of dyn-(1-8) were examined. The inhibitory effect of dyn-(1-8) on the tail-flick response was increased more than 100-fold by the i.t.v. pretreatment of rats with the three PIs. The inhibition produced by dyn-(1-8) in rats pretreated with any combination of two PIs was significantly smaller than that in rats pretreated with three PIs, indicating that any residual single peptidase could inactivate significant amounts of dyn-(1-8). The antagonistic effectiveness of naloxone, a relatively selective mu-opioid antagonist, indicates that dyn-(1-8)-induced inhibition of tail-flick response in rats pretreated with three PIs is mediated by mu-opioid receptors. Furthermore, mu-receptor-mediated inhibition induced by dyn-(1-8) was significantly greater than that produced by [Met5]-enkephalin in rats pretreated with three PIs. The data obtained in the present investigations together with those obtained in previous studies strongly indicate that dyn-(1-8) not only has well-known kappa-agonist activity but also has high mu-agonist activity.

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Section: Discussionmentioning

confidence: 94%

Effects of peptidase inhibitors on anti-nociceptive action of dynorphin-(1–8) in rats

Kitamura

Akahori

Yano

et al. 2000

Naunyn-Schmiedeberg's Arch Pharmacol

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“…It is not yet known, however, whether or not the hydrolysis of LE in the cerebrospinal fluid is also completely prevented by the three PIs. Low molecular weight opioid peptides such as ME and dyn (1-7) are shown to be hydrolyzed in cerebrospinal fluid mainly by aminopeptidase M that is inhibited by amastatin, and the other peptidase activities are suggested to be low in cerebrospinal fluid (17). Additionally, endopeptidase-24.11, which is inhibited by phosphoramidon, is indicated to play a key role in regulating the concentrations of neuropeptides, including enkephalins, in cerebrospinal fluid (18).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, endopeptidase-24.11, which is inhibited by phosphoramidon, is indicated to play a key role in regulating the concentrations of neuropeptides, including enkephalins, in cerebrospinal fluid (18). Three reports (1,17,18) suggest that the hydrolysis of LE administered i.t.v. is largely prevented in the presence of the three PIs: amastatin, captopril, and phosphoramidon.…”

Section: Discussionmentioning

confidence: 99%

Great Increase in Antinociceptive Potency of [Leu5]Enkephalin After Peptidase Inhibition

et al. 2008

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Abstract. Previous in vitro studies have shown that the degradation of [Leu 5 ]enkephalin during incubation with cerebral membrane preparations is almost completely prevented by a mixture of three peptidase inhibitors: amastatin, captopril, and phosphoramidon. The present in vivo study shows that the inhibitory effect of [Leu 5 ]enkephalin administered intra-third-ventricularly on the tail-flick response was increased more than 500-fold by the intra-third-ventricular pretreatment with the three peptidase inhibitors. The antinociceptive effect produced by the [Leu 5 ]enkephalin in rats pretreated with any combination of two peptidase inhibitors was significantly smaller than that in rats pretreated with the three peptidase inhibitors, indicating that any residual single peptidase could inactivate significant amounts of the [Leu 5 ]enkephalin. The present data, together with those obtained from previous studies, clearly demonstrate that amastatin-, captopril-, and phosphoramidon-sensitive enzymes play important roles in the inactivation of short endogenous opioid peptides, such as penta-, hepta-, and octa-peptides, administered intra-third-ventricularly to rats.

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“…It is not yet known, however, whether or not the hydrolysis of ME-RF in the cerebrospinal fluid is also completely prevented by the three PIs. Low molecular weight opioid peptides such as [Met 5 ]enkephalin (ME) and dynorphin A (1-7) are shown to be hydrolyzed in cerebrospinal fluid mainly by aminopeptidase M that is inhibited by amastatin, and the other peptidase activities are suggested to be low in cerebrospinal fluid (10). Additionally, endopeptidase-24.11, which is inhibited by phosphoramidon, is indicated to play a key role in regulating the concentrations of neuropeptides, including enkephalins, in cerebrospinal fluid (11).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, endopeptidase-24.11, which is inhibited by phosphoramidon, is indicated to play a key role in regulating the concentrations of neuropeptides, including enkephalins, in cerebrospinal fluid (11). Three reports (1,10,11) suggested that the hydrolysis of ME-RF administered intra-thirdventricularly is largely prevented in the presence of the three PIs: amastatin, captopril, and phosphoramidon. Therefore, the antinociceptive potency of ME-RF shown in the present study probably largely reflects the real potency of ME-RF itself.…”

Section: Discussionmentioning

confidence: 99%

The Enhancing Effects of Peptidase Inhibitors on the Antinociceptive Action of [Met5]Enkephalin-Arg6-Phe7 in Rats

et al. 2007

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Abstract. Previous in vitro studies have shown that the degradation of [Met 5]enkephalin-Arg 6 -Phe 7 during incubation with cerebral membrane preparations is largely prevented by a mixture of three peptidase inhibitors: amastatin, captopril, and phosphoramidon. The present in vivo study shows that the inhibitory effect of [Met 5 ]enkephalin-Arg 6 -Phe 7 administered intra-thirdventricularly on the tail-flick response was increased more than 1000-fold by the intra-thirdventricular pretreatment with three peptidase inhibitors. ]enkephalin-Arg 6 -Gly 7 -Leu 8 , and dynorphin A (1-8), administered intra-third-ventricularly to rats.

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N-terminal degradation of low molecular weight opioid peptides in human cerebrospinal fluid

Cited by 22 publications

References 34 publications

Effects of peptidase inhibitors on anti-nociceptive action of dynorphin-(1–8) in rats

Effects of peptidase inhibitors on anti-nociceptive action of dynorphin-(1–8) in rats

Great Increase in Antinociceptive Potency of [Leu5]Enkephalin After Peptidase Inhibition

The Enhancing Effects of Peptidase Inhibitors on the Antinociceptive Action of [Met5]Enkephalin-Arg6-Phe7 in Rats

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