Nociception, enkephalin content and dipeptidyl carboxypeptidase activity in brain of mice treated with exopeptidase inhibitors

Zhang, A.-Z.; Yang, Hongdian; Costa, E.

doi:10.1016/0028-3908(82)90004-1

Cited by 64 publications

(10 citation statements)

References 7 publications

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“…Simultaneous inhibition of enkephalinase and aminopeptidase M, the two peptidase activities responsible for hydrolysis of endogenous YGGFM, has been reported to increase the striatal level of this peptide (14,40), but this effect is of limited amplitude and is inconstant (unpublished observations). Because obtained under conditions of negligible YGGFM hydrolysis (see Materials and Methods).…”

Section: Resultsmentioning

confidence: 99%

“…This approach obviously requires a knowledge of the metabolic pathways of endogenous OPs. Endogenous enkephalins [Tyr-Gly-Gly-Phe-Met (YGGFM) and Tyr-GlyGly-Phe-Leu (YGGFL)] are degraded through (i) cleavage of the Tyr-Gly bond at residues 1 and 2 by a bestatin-sensitive aminopeptidase activity (14,15) (15,25) or in vivo (26,27), and its degradation is prevented by bestatin (15).…”

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confidence: 99%

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Steady-state level and turnover rate of the tripeptide Tyr-Gly-Gly as indexes of striatal enkephalin release in vivo and their reduction during pentobarbital anesthesia.

Llorens-Cortes¹,

Gros²,

Schwartz³

1986

Proc. Natl. Acad. Sci. U.S.A.

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Communicated by E. Costa, April 7, 1986 ABSTRACT Tyr-Gly-Gly (YGG) was recently shown to be an extraneuronal metabolite of opioid peptides derived from proenkephalin A, formed in brain by the action of "enkephalinase" (membrane metalloendopeptidase, EC 3.4.24.11) and degraded by aminopeptidases. The dynamic state of YGG in mouse striatum was studied by evaluating the changes in its level elicited by inhibitors of these peptidases. Inhibition of YGG synthesis by Thiorphan or acetorphan reduced YGG levels with a til2 (mean ± SEM) of 12 ± 2 min, indicating an apparent turnover rate (mean ± SEM) of 18 ± 2 pmol/mg of protein per hr. An apparent turnover rate of 18 ± 2 pmol/mg of protein per hr was derived from the rate of YGG accumulation elicited by the aminopeptidase inhibitor bestatin. In addition, accumulation of Tyr-Gly-Gly-Phe-Met (YGGFM) in an extrasynaptosomal fraction after blockade ofits degradation by Thiorphan and bestatin occurred at a rate of 18 ± 3 pmol/mg of protein per hr, which is likely to reflect the rate of enkephalin release in vivo. Hence, the three series of data suggest that striatal enkephalins rapidly turn over-e.g., with

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Steady-state level and turnover rate of the tripeptide Tyr-Gly-Gly as indexes of striatal enkephalin release in vivo and their reduction during pentobarbital anesthesia.

Llorens-Cortes¹,

Gros²,

Schwartz³

1986

Proc. Natl. Acad. Sci. U.S.A.

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“…Neurotransmitters/neuropeptides which predominantly facilitate nociception include the excitatory amino acid glutamate, histamine, cholecystokinin, melanocortin, and prostaglandins (Faris et al, 1983;Juan, 1981;Vrinten et al, 2000;Xu et al, 1995). Neurotransmitters/neuropeptides which predominantly inhibit nociception include GABA, glycine, vasopressin, oxytocin, adenosine, endogenous opioids, and endocannabinoids (Bernatzky et al, 1983;GarciaArraras et al, 1986;Le Bars et al, 1980;Nakamura et al, 1997;Sivam and Ho, 1983;Smith et al, 1998;Zhang et al, 1982). Brain regional alterations in levels of neurotransmitters unique to both facilitation or inhibition of nociception, the capacity of these neurotransmitters to bind to their respective receptors, or differential binding to receptor subtypes can alter nociceptive transmission and mediate SIA (Figure 2).…”

Section: Neurochemistry Of Siamentioning

confidence: 99%

Stress-induced analgesia

Butler

Finn

2009

Progress in Neurobiology

543

420

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Abbreviations: SIA, stress-induced analgesia; FCA, fear-conditioned analgesia; GABA, Ȗ-aminobutyric acid; HA, high analgesia; LA, low analgesia; fMRI, functional magnetic resonance imaging; DNIC, diffuse noxious inhibitory control; PAG, periaqueductal grey; RVM, rostroventral medulla; 5-HT, 5-hydroxytryptamine; CB 1 , cannabinoid type 1; CB 2 , cannabinoid type 2; NMDA, N-methyl-D-aspartic acid; AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; mGluR, metabotropic glutamate receptor; NK1, neurokinin 1; SP, substance P; 2-AG, 2-arachidonoylglycerol; FAAH, fatty acid amide hydrolase; MGL, monoacylglycerol lipase; HPA, hypothalamo-pituitary-adrenal; ACTH, adrenocorticotropic hormone 3 ABSTRACT For over 30 years, scientists have been investigating the phenomenon of pain suppression upon exposure to unconditioned or conditioned stressful stimuli, commonly known as stress-induced analgesia. These studies have revealed that individual sensitivity to stressinduced analgesia can vary greatly and that this sensitivity is coupled to many different phenotypes including the degree of opioid sensitivity and startle response. Furthermore, stress-induced analgesia sensitivity can vary a great deal depending on age, gender, and prior experience to stressful, painful, or other environmental stimuli. Stress-induced analgesia is mediated by activation of the descending inhibitory pain pathway.Pharmacological and neurochemical studies have demonstrated involvement of a large number of neurotransmitters and neuropeptides. In particular, there are key roles for the HQGRJHQRXV RSLRLG PRQRDPLQH FDQQDELQRLG Ȗ-aminobutyric acid and glutamate systems. The study of stress-induced analgesia has enhanced our understanding of the fundamental physiology of pain and stress and has been a useful approach for uncovering new therapeutic targets for the treatment of pain and stress-related disorders.4

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“…With cell-free and intact-cell preparations, the liberation of Tyr is the major mode of enkephalin degradation for its inactivation [38,39]. In addition, aminopeptidase inhibitor, bestatin or puromycin produces a dose-related, naloxone-reversible, analgesic effect [40][41][42].…”

Section: Nh 2 -Terminal Hydrolysismentioning

confidence: 99%

Brain-Specific Aminopeptidase: From Enkephalinase to Protector Against Neurodegeneration

Hui

2007

Neurochem Res

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The major breakthrough discovery of enkephalins as endogenous opiates led our attempts to determine their inactivation mechanisms. Because the NH2-terminal tyrosine is absolutely necessary for the neuropeptides to exert analgesic effects, and aminopeptidase activities are extraordinarily high in the brain, a specific "amino-enkephalinase" should exist. Several aminopeptidases were identified in the central nervous system during the search. In fact, our laboratory found two novel neuron-specific aminopeptidases: NAP and NAP-2. NAP is the only functionally active brain-specific enzyme known. Its synaptic location coupled with its limited substrate specificity could constitute a "functional" specificity and contribute to enkephalin-specific functions. In addition, NAP was found to be essential for neuron growth, differentiation, and death. Thus, aminopeptidases are likely important for mental health and neurological diseases. Recently, puromycin-sensitive aminopeptidase (PSA) was identified as a modifier of tau-induced neurodegeneration. Because the enzymatic similarity between PSA and NAP, we believe that the depletion of NAP in Alzheimer's disease (AD) brains plays a causal role in the development of AD pathology. Therefore, use of the puromycin-sensitive neuron-aminopeptidase NAP could provide neuroprotective mechanisms in AD and similar neurodegenerative diseases.

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Nociception, enkephalin content and dipeptidyl carboxypeptidase activity in brain of mice treated with exopeptidase inhibitors

Cited by 64 publications

References 7 publications

Steady-state level and turnover rate of the tripeptide Tyr-Gly-Gly as indexes of striatal enkephalin release in vivo and their reduction during pentobarbital anesthesia.

Steady-state level and turnover rate of the tripeptide Tyr-Gly-Gly as indexes of striatal enkephalin release in vivo and their reduction during pentobarbital anesthesia.

Stress-induced analgesia

Brain-Specific Aminopeptidase: From Enkephalinase to Protector Against Neurodegeneration

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