Transport of Opioid Peptides into the Central Nervous System

作者: Richard D. Egleton , Thomas J. Abbruscato , Sarah A. Thomas , Thomas P. Davis

DOI: 10.1021/JS980062B

关键词: Blood–brain barrierBiochemistryOpioid peptideBiphalinPeptide hormoneChemistryPeptideEnkephalinCell biologyGastric motilityNeuropeptide

摘要: Peptide hormones and neurotransmitters play crucial roles in the maintenance of physiological function at both cellular organ level. Although peptide neuropharmaceuticals have enormous potential treatment disease states, blood–brain barrier (BBB) generally prevents entry peptides into brain either by enzyme degradation or specific properties BBB. Peptides that act opioid receptors are currently being designed for analgesia to reduce unwanted side effects associated with morphine, such as addiction inhibition gastric motility. It has been focus our group produce stabile analogues Met-enkephalin, lead without effects. In this paper we present methodologies used elucidate transport mechanisms three across Using a primary endothelial cell culture model BBB, situ perfusion, kinetic analysis show D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) crosses BBB via diffusion, [D-penicillamine2,5]-enkephalin uses combination diffusion saturable mechanism, biphalin ([Tyr-D-Ala-Gly-Phe-NH]2) large neutral amino acid carrier. Understanding will aid rational design targeted brain.

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