Deltorphins

Delta ring Delta vehicles Deltorphin Deltorphins Deluxe phosphors Dember effect... 

Another class of 5-selective peptides, isolated from extracts of frog skin, is the deltorphins. These compounds are based on the stmcture... 

Selective agonists DAMGO DPDPE, D-ala2-deltorphin II Enadoline, U-50488 ... 

Erspamer Y, Melchiorri P, Falconieri-Erspamer G, et al. Deltorphins a family of naturally occurring peptides with high affinity and selectivity for opioid binding sites. Proc Natl Acad Sci USA 1989 86 5188-5192. 

DAMME [D-Ala2,MePhe4,Met(0)-ol5]enkephalin [D-Me. Pro enkephalinamide [D-Ala2]deltorphin I [D-Ala2]deltorphin II [D-Ala2]dermorphin... 

Erspamer, V., Melchiorri, P., Falconieri-Erspamer, G., Negri, L., Corsi, R., Severin , C., Barra, D., Simmaco, M., Kreil, G. Deltorphins a family of naturally occurring peptides with high affinity and selectivity for Sopioid binding sites, Proc. Natl. Acad. Sci. USA 1989, 86, 5188-5192. 

I.c.v. and i.t. administration of the 5 opioid agonist deltorphin II in rodents inhibits diarrhea and colonic bead expulsion in a dose-dependent manner but does not delay small intestine transit time. 5 agonists have been found to mediate mainly antisecretory effects and influence gut motility only marginally. These effects can be antagonized by pretreatment with NTI (Shook et al. 1989). 

Lazarus, L.H., Bryant, S.D., Cooper, P.S., Salvadori, S. What peptides these deltorphines be, Prog. Neurobiol. 1999, 57, 377-420. 

D-Ala2]Deltorphin I [D-Ala2,Glu4] Deltorphin (Deltorphin II)... 

The selectivity of currently used delta agonists may not be sufficient to avoid mu receptor activation in vivo. As an example, one study showed that DPDPE (selectivity delta/mu 100-fold) injected either ICV or ITH was less active in the mu receptor mutant than deltorphin (selectivity mu/delta 10,000-fold) [60]. This suggests that, in WT mice the less delta selective compound recruits mu receptors to produce analgesia in the tail flick and hot plate tests under their experimental conditions. 

Delta receptors nevertheless mediate some delta agonist induced analgesia, as suggested by reduced DPDPE and deltorphin activity in the DOR mutant after ITH applications [52], or enhanced antinociceptive activity in MOR mutants subjected to CFA inflammation [65]. Delta receptors also depress respiratory neurons in slice preparations [66] and mediate SNC80-evoked convulsions [67]. 

In addition to in vitro cell models, opioid agonists could induce the rapid endocytosis of the receptor in organo cultures or primary neuronal cultures, and also neurons in vivo. Treatment of longitudinal muscle-myenteric plexus preparation or the primary hippocampal neuron cultures with DAMGO resulted in internalization of the mu opioid receptor [146,147]. Similar observation was obtained with fluorescently labeled opioid peptides Fluo-dermorphin and Fluo-deltorphin [148]. Within 15 min of an intra-peritoneal injection of etorphine, mu opioid receptor immunoreactivity was observed in the endosomal structures of the myenteric neurons of guinea pig ileum [149]. Again, rapid clustering of a spliced variant of mu opioid receptor MOR-1C was observed in the lateral septum of the mouse after intracere-... 

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