By F Benedetti; Christoph Stein; et al

ISBN-10: 3540338233

ISBN-13: 9783540338239

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1999). For the chemoattractant C5a receptor, another GPCR, it was suggested that the ECL act as a filter and regulate the ability of the ligand to interact with the binding pocket (Massotte and Kieffer 2005). Evidence supports the notion that, in addition to guiding ligands on their way to the binding pocket, the ECL may regulate the “on-off” transition in the absence of ligands (Klco et al. 2005). 2 Transmembrane Domains TM residues within the lipophilic environment of the cell membrane are key in ligand recognition and/or signal transduction and are expected to be oriented toward a relatively hydrophilic central cavity (Surratt et al.

Zöllner · C. Stein tions of endogenous opioid peptides in various central and peripheral tissues is ongoing but has not resulted in clinical applications for pain treatment so far (Roques 2000). 2 Exogenous Ligands Exogenous opioid ligands can be classified into three groups: full agonists, partial agonists/antagonists, and full antagonists. The standard to which all other opioid analgesics are compared is morphine. Although the alkaloid morphine was isolated in the early 1800s the structure of morphine was identified only in 1925 by Gullard and Robinson (Fig.

After synthesis in the DRG, opioid receptors are transported to the peripheral nerve terminals of primary afferent neurons (Hassan et al. 1993; Fig. 4c). Opioid receptors are also expressed by neuroendocrine (pituitary, adrenals), immune, and ectodermal tissues (Slominski et al. 2000). Although opioids increase potassium currents in the CNS it is still controversial whether this occurs in DRG neurons. Rather, it was shown that the modulation of Ca2+ currents is the principal mechanism for the inhibitory effect of opioids on sensory neurons (Akins and Opioids 45 McCleskey 1993).

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