Metabolism of galanin and galanin (1-16) in isolated cerebrospinal fluid and spinal cord membranes from rat.
The occurrence of galanin (GAL) in the spinal cord and reports suggesting that it acts as an endogenous inhibitory spinal modulator in sensory/noxious transmission, have focused interest on its metabolism in the spinal cord. The metabolic half-lives and degradation patterns of GAL(1-29) and the high affinity N-terminal fragment GAL(1-16), were determined in isolated cerebrospinal fluid (CSF) from rats, and analysed by reverse phase HPLC. The half-lives for GAL(1-29) and GAL(1-16) in isolated rat CSF at 37 degrees C were 120 min and 60 min, respectively. The first degradation products which we could isolate and identify of GAL(1-16) were: GAL(3-16) and GAL(3-12) and for GAL(1-29): GAL(1-5) and GAL(1-4), all without affinity to spinal galanin receptors. Degradation studies of GAL(1-29) and GAL(1-16) in a spinal cord membrane preparation, in absence or presence of different protease inhibitors: E-64, pepstatin A, 3,4-DCI, bestatin, phosphoramidon, kelatorphan and thiorphan, or metal chelators: EDTA, EGTA and o-phenanthrolin, suggest that a phosphoramidon sensitive zinc-metalloprotease is mainly responsible for the degradation of GAL(1-29) and GAL(1-16), since both o-phenanthrolin (0.3 mM) and phosphoramidon (920 microM) substantially prolong their half-lives.
Department of Neurochemistry and Neurotoxicology, Stockholm University, Sweden.
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K
Bedecs
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U
Langel
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T
Bartfai
D000595:Amino Acid Sequence; D000818:Animals; D019004:Galanin / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D008161:Lumbosacral Region; D008297:Male; D008566:Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*
D010446:Peptide Fragments; C062019:galanin (1-16); D019004:Galanin