On the degradation of the deltorphin peptides by plasma and brain homogenate.
The peptidase-resistance of deltorphins (DEL-A, H-Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2) and (DEL-C, H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2), highly selective and potent agonists of the delta opioid receptor, were investigated in vitro. DEL-C was fully resistant to degradation by rat plasma and strongly resistant to degradation by rat brain homogenates. DEL-A was cleaved with a half-life of 131.6 min upon incubation with plasma, and 57.4 min with rat brain homogenates. N-terminal truncated sequences of DEL-A and -C with free carboxyl groups, were also analyzed for receptor binding activity using [3H] DADLE for delta sites and [3H] DAGO for mu sites. The high enzymatic stability associated with deltorphins and their degradation products may make them prime candidates to characterize the role of delta-receptors in vivo.
Marastoni
M
M
Department of Pharmaceutical Sciences, University of Ferrara, Italy.
Tomatis
R
R
Balboni
G
G
Salvadori
S
S
Lazarus
L H
LH
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000097:blood / Q000378:metabolism*; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013574:Synaptosomes / Q000378:metabolism
D000596:Amino Acids; D009842:Oligopeptides; D010455:Peptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C059567:deltorphin