Targets for SMR1-pentapeptide suggest a link between  the circulating peptide and mineral transport

Rougeot, Catherine; Vienet, Raymond; Cardona, Ana; Doledec, L. Le; Grognet, Jean‐Marc; Rougeon, François

doi:10.1152/ajpregu.1997.273.4.r1309

Cited by 25 publications

(48 citation statements)

References 18 publications

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“…Rat sialorphin is an endocrine peptide signal whose expression is activated by androgen regulation and whose secretion is stimulated under adrenergic-mediated response to environmental stress in male rats. It is a physiological inhibitor of the membrane-anchored rat NEP activity and is a powerful inhibitor of pain sensation in rats (9)(10)(11)(12)(13). To our knowledge, bovine spinorphin and rat sialorphin are the only identified natural enkephalin catabolism inhibitors inducing antinociception in mammals (8,13).…”

mentioning

confidence: 99%

Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways

Wisner

Dufour

Messaoudi³

et al. 2006

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

161

148

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Mammalian zinc ectopeptidases play important roles in turning off neural and hormonal peptide signals at the cell surface, notably those processing sensory information. We report here the discovery of a previously uncharacterized physiological inhibitor of enkephalininactivating zinc ectopeptidases in humans, which we have named Opiorphin. It is a QRFSR peptide that inhibits two enkephalin-catabolizing ectoenzymes, human neutral ecto-endopeptidase, hNEP (EC 3.4.24.11), and human ecto-aminopeptidase, hAP-N (EC 3.4.11.2). Opiorphin displays potent analgesic activity in chemical and mechanical pain models by activating endogenous opioid-dependent transmission. Its function is closely related to the rat sialorphin peptide, which is an inhibitor of pain perception and acts by potentiating endogenous -and ␦-opioid receptor-dependent enkephalinergic pathways. Here we demonstrate the functional specificity in vivo of human Opiorphin. The pain-suppressive potency of Opiorphin is as effective as morphine in the behavioral rat model of acute mechanical pain, the pin-pain test. Thus, our discovery of Opiorphin is extremely exciting from a physiological point of view in the context of endogenous opioidergic pathways, notably in modulating mood-related states and pain sensation. Furthermore, because of its in vivo properties, Opiorphin may have therapeutic implications.dual neutral endopeptidase͞aminopeptidase N inhibitor ͉ human saliva ͉ pain ͉ peptide mediator ͉ enkephalins Z inc metal ectopeptidases control the receptor-dependent activity of neural and hormonal mediators involved in the regulation of important physiological functions in mammals. They are located at the surface of cells in nervous and systemic tissues and catalyze postsecretory processing or metabolism of neuropeptides and regulatory peptides (1, 2). Prominent among these neuronal and͞or hormonal peptide signals are substance P (SP) and enkephalins, which are implicated in the receptor-dependent modulation of behavioral adaptive responses to stressful or threatening environmental stimuli. They notably regulate spinal processing of nociceptive information and analgesic mechanisms, emotional and͞or motivational responses, anxiety, aggression, and neuroimmune inflammatory phenomena (3-6).Because of the physiological importance and the critical role of zinc ectopeptidases in modulating the functional potency of downstream neuronal and hormonal signals, it is essential to focus on what controls their activity and, as a consequence, the overall regulatory cascade. The discovery of upstream regulators of ectopeptidase activity also is exciting from physiopathological and therapeutic points of view because of the potential for developing new candidate drugs. A brain-specific heptapeptide named spinorphin was isolated and characterized from bovine spinal cord based on its inhibitory activity toward enkephalin-degrading ectoenzymes, such as neutral endopeptidase (NEP; EC 3.4.24.11) and aminopeptidase N (AP-N; EC 3.4.11.2) (7,8). In addition, we characterized rat sial...

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mentioning

confidence: 99%

Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways

Wisner

Dufour

Messaoudi³

et al. 2006

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

161

148

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“…The quantitative determination of the radioactivity in whole-body sections was carried out by ␤-imager 2200 (Biospace, Paris; refs. 8, 10, and 11 8. At different time points after peptide administration (2-120 min), 250 l of blood sample were withdrawn, and the entire urinary bladder content was collected at the last selected point.…”

Section: Materials and Methods Peptide Constructs The Synthesis Of 5mentioning

confidence: 99%

“…In the present study, we have mapped potential peripheral targets for the HB-19 pseudopeptide by examining in vivo the gross tissue distribution of the radiolabeled pseudopeptide with whole rat body mapping (8). The visual imaging of the entire animal by ␤-radio imaging provided a convenient and efficient technique to examine and record simultaneously the uptake of HB-19 in a large number of tissues and compartments.…”

Section: T He Human Immunodeficiency Virus (Hiv) Is An Envelopedmentioning

confidence: 99%

“…The chromatographic characteristics of the labeled pseudopeptide in the plasma, urine, and in different tissues were assessed by RP-HPLC (8). At selected times (4,8, and 24 h) after i.v.…”

Section: Chromatographic Characterization Of the Radioactive Pseudopementioning

confidence: 99%

“…At selected times (4,8, and 24 h) after i.v. injection of 20 g (50 Ci) of [ 3 H]-labeled HB-19, urine was collected and the rats were anesthetized and killed by cardiac blood puncture.…”

Section: Chromatographic Characterization Of the Radioactive Pseudopementioning

confidence: 99%

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The anti-HIV pentameric pseudopeptide HB-19 is preferentially taken up in vivo by lymphoid organs where it forms a complex with nucleolin

Krust

Vienet

Cardona

et al. 2001

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

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1-Substituted sialorphin analogues—synthesis, molecular modelling and in vitro effect on enkephalins degradation by NEP

et al. 2019

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Rat sialorphin (Gln-His-Asn-Pro-Arg) is a natural blocker of neprilysin (NEP) that belongs to the family of endogenous opioid peptide-degrading enzymes. Studies have confirmed the efficiency of sialorphin in blocking the activity of NEP, both in vitro and in vivo. It has been demonstrated that this inhibitor has a strong analgesic, anti-inflammatory, immunological and metabolic effect either directly or indirectly by affecting the level of Met/Leu-enkephalins. In this work, sialorphin and their 12 analogues were synthesised using the solid-phase method. The effect of the peptides on the degradation of Metenkephalin by NEP and metabolic degradation in human plasma was investigated in vitro. We show that the change in the N-terminal amino acid configuration from l to d in almost all peptides, except d-Arg-His-Asn-Pro-Arg (peptide XI), led to the abolition of their inhibitory activity. With molecular modelling technique we explained the structural properties of the l and d-arginine located on the N-terminal part of the peptide. The detailed analysis of the protein binding pocket allowed us to explain why d-arginine is so unique among all d residues. Peptide XI showed the highest stability among the tested peptides in human plasma. For instance sialorphin after a 2-hour incubation in human plasma was almost completely decomposed, while the level of peptide XI dropped to 45% after 48 h under these conditions.

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Targets for SMR1-pentapeptide suggest a link between the circulating peptide and mineral transport

Cited by 25 publications

References 18 publications

Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways

Human Opiorphin, a natural antinociceptive modulator of opioid-dependent pathways

The anti-HIV pentameric pseudopeptide HB-19 is preferentially taken up in vivo by lymphoid organs where it forms a complex with nucleolin

1-Substituted sialorphin analogues—synthesis, molecular modelling and in vitro effect on enkephalins degradation by NEP

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