Dynorphins interaction

The EOPs have been directly implicated in the pathophysiology of TS syndrome. Haber and co-workers (1986) reported decreased levels of dynorphin A(l-17) immunoreactivity in striatal fibers projecting to the GP in postmortem material from a small number of Tour-ette s patients. This observation, coupled with the neu-roanatomic distribution of dynorphin, its broad range of motor and behavioral effects, and its modulatory interactions with striatal dopaminergic systems, suggest that dynorphin might have a key role in the patho-biology of TS. However, subsequent studies have failed to confirm these initial observations (van Wattum et al., 1999). 

II. Interaction Between Dynorphins and the NMDA Receptor Ion-Channel Complex... 

Subsequently, numerous peptides with opioid-like effects have been found in the central nervous system and in peripheral tissues. These endogenous opioid peptides vary in size, but their amino terminals mostly share a similar enkephalin sequence of amino acids. Currently, four separate, individually gene-derived families of endogenous opioid peptides are recognized the endorphins, the enkephalins, the dynorphins and the endomorphins [17a], -Endorphin interacts predominantly with n and 6 receptors, Leu-enkephalin and Met-enkephalin interact predominantly with 5 receptors, dynorphin shows preference for k receptors [17b], while endomorphins 1 and 2 exhibit... 

The possible conformations of dynorphin A have been studied by a variety of spectral techniques (see Ref 753 for a review). Like other linear peptides, a variety of conformations have been observed for dynorphin A, which depend on the experimental conditions. Schwyzer (755) proposed a membrane-assisted model for dynorphin s interaction with k receptors, in which theN-terminal "message" sequence adopts an a-helical structure from residues 1-9 when it binds to the receptor. NMR studies of dynorphin A bound to dode-cylphosphocholine micelles (756, 757) observed a helical structure in the N-terminal portion of the peptide, supporting this pro-... 

A novel endogenous opioid peptide with significant sequence homology to dynorphin A was alternatively termed nociceptin or orphanin FQ (now termed N/OFQ Table 21-1). The substitution of Phe for Tyr in the opioid motif is sufficient to abolish interactions with the three classical opioid peptide receptors. N/OFQ has behavioral and pain modulatory properties distinct from those of the three classical opioid peptides. 

Fig. 5.4 Interactions among dynorphin, gluteimate, and Idnin receptors in spinal cord injury. Dinorphin (D) glutamate (Glu) arginine (Arg) nitric oxide synthase (NOS) nitric oxide (NO) superoxide (O2 ) peroxynitrite (ONOO ) phosphatidylcholine (PtdCho) cytosolic phosphoUpase A2 (CPLA2) arachidonic acid (ARA) phospholipase C (PLC) diacylglycerol (DAG) inositol 1,4,5-trisphosphate (InPs) endoplasmic reticulum (ER) platelet-activating factor (RAF) reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE)...

In a series of ingenious experiments on ACTH and dynorphin Schwyzer has also shown that their pharmacological potency and hydrophobic membrane interactions are critically dependent on the covalent linkage of message and address to form amphiphilic molecules. Amphiphilicity is caused in these cases by the amphiphilic primary structures, in contrast to the amphiphilicity resulting from the secondary and tertiary structure of some other peptide hormones. Such an amphiphilicity was postulated recently by Kaiser and Kezdy [32] for hormones such as insulin and -endorphin [33]. 

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