Processing of prodynorphin at single and paired basic residues in porcine neurointermediate lobe

Kilpatrick, Daniel L.; Eisen, Milton J.; Ezra, Elhanan; Udenfriend, Sidney

doi:10.1016/0024-3205(83)90452-6

Cited by 17 publications

(3 citation statements)

References 7 publications

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“…1997). The differences in results probably arise from the fact that the previous in vitro study used homogenized tissue; homogenization may lead to the release of prohormone convertase enzymes, predominantly localized intracellularly, which can process the paired basic residues Arg 6 ‐Arg 7 , as is found in extracts from the pituitary (Kilpatrick et al . 1983).…”

Section: Discussionmentioning

confidence: 99%

“…Homogenates from both the striatum and substantia nigra of rats showed relatively low levels of Dyn A(1-17) biotransformation, with the only detected product being Dyn A(1-5) (leucine enkephalin) (Sandin et al 1997). The differences in results probably arise from the fact that the previous in vitro study used homogenized tissue; homogenization may lead to the release of prohormone convertase enzymes, predominantly localized intracellularly, which can process the paired basic residues Arg 6 -Arg 7 , as is found in extracts from the pituitary (Kilpatrick et al 1983).…”

Section: -Dynmentioning

confidence: 99%

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Dynorphin A(1–17) biotransformation in striatum of freely moving rats using microdialysis and matrix‐assisted laser desorption/ionization mass spectrometry

Reed

Zhang²,

Chait

et al. 2003

Journal of Neurochemistry

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The biotransformation of the opioid peptide dynorphin A(1-17) was investigated in striatum of freely moving Fischer rats, by direct infusion of this peptide, followed by recovery of the resulting biotransformation products via microdialysis and identification using matrix-assisted laser desorption/ionization mass spectrometry. The observed peptides are consistent with enzymatic cleavage at the Arg 7 -Ile 8 position of dynorphin A(1-17), followed by terminal degradation of the resulting dynorphin A(1-7) and dynorphin A(8-17) peptides. Unexpectedly, novel post-translational modifications were found on C-terminal fragments of dynorphin A(1-17). Using tandem mass spectrometry, a covalent modification of mass 172 Da, the nature of which is not understood, was found on the tryptophan residue of C-terminal fragments (Trp 14 ). Additional modifications, of mass 42 and 113 Da, were also found on the N-terminus (Ile 8 or Pro 10 ) of these same C-terminal fragments. The role of these modifications of C-terminal fragments has not yet been characterized.

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Section: Discussionmentioning

confidence: 99%

Section: -Dynmentioning

confidence: 99%

Dynorphin A(1–17) biotransformation in striatum of freely moving rats using microdialysis and matrix‐assisted laser desorption/ionization mass spectrometry

Reed

Zhang²,

Chait

et al. 2003

Journal of Neurochemistry

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“…Since the small enkephalin-containing peptides are preferred as substrates by the enzyme or enzymes acting at the pair of basic residues serving as signals for processing, the involvement of other enzymes would need to be postulated. Indeed, evidence indicating that Leu-enk might be derived from smaller prodynorphin-derived peptides has been presented (Kilpatrick et al, 1983;Zamir et al, 1984a,b). Furthermore, examination of the distribution of prodynorphin-derived peptides in different brain regions and the pituitary has led to the conclusion that processing of prodynorphin is not uniform in all regions.…”

Section: Discussionmentioning

confidence: 99%

Synaptosomal Membrane‐Bound Form of Endopeptidase‐24.15 Generates Leu‐Enkephalin from Dynorphin _1‐8, α‐ and β‐Neoendorphin, and Met‐Enkephalin from Met‐Enkephalin‐Arg⁶‐Gly⁷‐Leu

Acker

Molineaux

Orłowski

1987

Journal of Neurochemistry

126

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Brain contains a membrane-bound form of endopeptidase-24.15, a metalloendopeptidase predominantly associated with the soluble protein fraction of brain homogenates. Subcellular fractionation of the enzyme in rat brain showed that 20-25% of the total activity is associated with membrane fractions including synaptosomes. Solubilization of the enzyme from synaptosomal membranes required the use of detergents or treatment with trypsin. The specific activity of the enzyme in synaptosomal membranes measured with tertiary-butoxycarbonyl-Phe-Ala-Ala-Phe-p-aminobenzoate as substrate was higher than that of endopeptidase-24.11 ("enkephalinase"), a membrane-bound zinc-metalloendopeptidase believed to function in brain neuropeptide metabolism. Purified synaptosomal membranes converted efficiently dynorphin1-8, alpha- and beta-neoendorphin into leucine enkephalin and methionine-enkephalin-Arg6-Gly7-Leu8 into methionine enkephalin in the presence of captopril, bestatin, and N-[1-(R,S)-carboxy-2-phenylethyl]-Phe-p-aminobenzoate, inhibitors of angiotensin converting enzyme (EC 3.4.15.1), aminopeptidase (EC 3.4.11.2), and membrane-bound metalloendopeptidase (EC 3.4.24.11), respectively. The conversion of enkephalin-containing peptides into enkephalins was virtually completely inhibited by N-[1-(R,S)-carboxy-2-phenylethyl]-Ala-Ala-Phe-p-aminobenzoate, a specific active-site-directed inhibitor of endopeptidase-24.15, indicating that this enzyme was responsible for the observed interconversions. The data indicate that synaptosomal membranes contain enzymes that can potentially generate and degrade both leucine- and methionine-enkephalin.

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Immunocytochemical distribution of met‐enkephalin‐Arg⁶‐Gly⁷‐Leu⁸ in the rat lower brainstem

Murakami

Okamura

Yanaihara

et al. 1987

J of Comparative Neurology

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The distribution of methionine-enkephalin-Arg6-Gly7-Leu8, a unique peptide derived from proenkephalin A in the rat brainstem, was studied immunocytochemically by using a highly specific antiserum to this octapeptide sequence. Immunoreactive perikarya with various shapes and sizes were detected in many regions of the rat brainstem. Dense accumulation of immunoreactive perikarya and fibers was seen in the nuclei associated with special sensory and visceral functions, such as the interpeduncular nucleus, the parabrachial nucleus, the nucleus of the solitary tract, and the nucleus of the spinal tract of the trigeminal nerve. Clusters of methionine-enkephalin-Arg6-Gly7-Leu8-like immunoreactive perikarya and fibers were observed in certain areas considered to play a role in nociception and analgesia, such as the central gray of the midbrain central gray and the raphe magnus nucleus. Some methionine-enkephalin-Arg6-Gly7-Leu8-like immunoreactive perikarya were distributed in the lateral reticular nucleus, the nucleus of the solitary tract, and the raphe magnus nucleus, where monoaminergic neurons were also detected. In addition to the previously reported enkephalinergic cells, we found many methionine-enkephalin-Arg6-Gly7-Leu8 containing neurons; the rostral and caudal linear nucleus of raphe, the median raphe nucleus, entire length of the raphe magnus nucleus, the medial longitudinal fasciculus, the cuneate nucleus, the external cuneate nucleus, the gracile nucleus, and the area postrema. The wide distribution of this octapeptide-like immunoreactivity reflected neurons expressing the preproenkephalin A gene distributed more widely than previously reported and that innervated many regions.

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Processing of prodynorphin at single and paired basic residues in porcine neurointermediate lobe

Cited by 17 publications

References 7 publications

Dynorphin A(1–17) biotransformation in striatum of freely moving rats using microdialysis and matrix‐assisted laser desorption/ionization mass spectrometry

Dynorphin A(1–17) biotransformation in striatum of freely moving rats using microdialysis and matrix‐assisted laser desorption/ionization mass spectrometry

Synaptosomal Membrane‐Bound Form of Endopeptidase‐24.15 Generates Leu‐Enkephalin from Dynorphin _1‐8, α‐ and β‐Neoendorphin, and Met‐Enkephalin from Met‐Enkephalin‐Arg⁶‐Gly⁷‐Leu

Immunocytochemical distribution of met‐enkephalin‐Arg⁶‐Gly⁷‐Leu⁸ in the rat lower brainstem

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Processing of prodynorphin at single and paired basic residues in porcine neurointermediate lobe

Cited by 17 publications

References 7 publications

Dynorphin A(1–17) biotransformation in striatum of freely moving rats using microdialysis and matrix‐assisted laser desorption/ionization mass spectrometry

Dynorphin A(1–17) biotransformation in striatum of freely moving rats using microdialysis and matrix‐assisted laser desorption/ionization mass spectrometry

Synaptosomal Membrane‐Bound Form of Endopeptidase‐24.15 Generates Leu‐Enkephalin from Dynorphin 1‐8, α‐ and β‐Neoendorphin, and Met‐Enkephalin from Met‐Enkephalin‐Arg6‐Gly7‐Leu

Immunocytochemical distribution of met‐enkephalin‐Arg6‐Gly7‐Leu8 in the rat lower brainstem

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Synaptosomal Membrane‐Bound Form of Endopeptidase‐24.15 Generates Leu‐Enkephalin from Dynorphin _1‐8, α‐ and β‐Neoendorphin, and Met‐Enkephalin from Met‐Enkephalin‐Arg⁶‐Gly⁷‐Leu

Immunocytochemical distribution of met‐enkephalin‐Arg⁶‐Gly⁷‐Leu⁸ in the rat lower brainstem