Delta opioid receptor studies

Human delta opioid receptor Functional studies on stably transfected Chinese hamster ovary cells after acute and chronic treatment with the selective non-peptidic agonist SNC-80. J Pharmacol Exp Ther 1996 278 1083-1089. 

The geometric isomers 464 and 467 of 5(47/)-oxazolones prepared from acetophenones can be separated. Alternatively, the mixture can be isomerized under the appropriate reaction conditions to obtain the pure of (Z) or ) isomer. Each isomer can be converted to a pair of enantiomers 466 and 469 (only one enantiomer shown) (Scheme 7.152). The p-methyl phenylalanine analogues thus obtained are constrained phenylalanines and the effect of incorporation of a p-MePhe or p-MeTyr residue on the biological properties of H-Tyr-Tic-Phe-Phe-NH2 (TIPP, where Tic = l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) a delta opioid receptor antagonist, has been studied. ... 

House, R.V., Thomas, P.T., Bhargava, H.N. A comparative study of immunmodulation produced, by in vitro exposure to delta opioid receptor agonist peptides, Peptides 1996, 17, 75-81. 

One of the most studied effectors regulated by the delta opioid receptor is the adenylyl cyclase. Opioid agonist inhibition of the icAMP production... 

IN VIVO STUDIES OF DELTA OPIOID RECEPTOR G-PROTEIN INTERACTIONS... 

Further studies in mouse vas deferens indicated that DPI-3290 is also active at mu opioid receptors. The intrinsic activity of DPI-3290 at mu opioid receptors was determined in the presence of the highly selective delta opioid receptor antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH) (3 pM) and the selective kappa opioid receptor antagonist nor-BNI (15 nM). Under these conditions, DPI-3290 again caused concentration-dependent inhibition of muscle contraction with a corresponding IC50 value of 6.2 2.0 nM. Although far less potent at kappa opioid receptors in comparison to its intrinsic activity at mu... 

Pharmacological studies with selective agonists have shown that opioid control of intestinal electrolyte transport is predominantly mediated by delta opioid receptors [58], while the gastrointestinal propulsion is under the control of mu receptors [59,60]. The antidiarrheal effects of NEP inhibitors, such as acetorphan, the prodrug of thiorphan, have been compared to those of an opiate agonist, loperamide, in a model of castor oil-induced diarrhea in rats. When administered peripherally, they produced a delayed onset of diarrhea with no reduction in the gastrointestinal transit [61,62], as is commonly observed with loperamide [63],... 

On the other hand, a number of studies have shown that morphine and opioid peptides could have cardioprotective effects toward ischemic processes and may be able to reduce the size of infarct [72,73]. These effects seem to involve the activation of delta opioid receptors, the localization of which remains unknown. In addition, enkephalin-degrading enzyme inhibitors, such as acetorphan and, particularly, RB 101, have also been demonstrated to decrease the susceptibility to the arrhythmogenic action of epinephrine. Thus RB 101 completely prevented the ventricular tachycardia, fibrillation, and repetitive ventricular extrasystoles induced by epinephrine (Maslov et al., unpublished data). These effects were reversed by the selective delta antagonist ICI 174,864. 

PENK), prodynorphin (PDYN), and pro-opiomelanocortin (POMC) [13-15]. PENK was originally discovered in bovine adrenal cortex and pig brain, where enkephalin biosynthesis was elucidated [13]. It contains one copy of Leu-enkephalin, four copies of Met-enkephalin, and one copy each of a Met-enkephalin C-terminal-extended heptapeptide and octapeptides, all flanked by basic dipeptides, where processing generally takes place. The primary identification of delta opioid receptors was a direct consequence of the discovery of these enkephalins [16]. These peptides were first examined for their potency at opioid receptors present in the guinea pig ileum and mouse vas deferens bioassays. The result of these studies shows that enkephalins are acting at a different receptor in the mouse vas deferens than the guinea pig ileum and this receptor for enkephalins was defined as the elimination of the delta opioid receptor [17]. 

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