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Title: (D-Pen2,4 prime -125I-Phe4,D-Pen5)enkephalin: A selective high affinity radioligand for delta opioid receptors with exceptional specific activity

Abstract

(D-Pen2,4{prime}-125I-Phe4,D-Pen5)enkephalin ((125I)DPDPE) is a highly selective radioligand for the delta opioid receptor with a specific activity (2200 Ci/mmol) that is over 50-fold greater than that of tritium-labeled DPDPE analogs. (125I)DPDPE binds to a single site in rat brain membranes with an equilibrium dissociation constant (Kd) value of 421 {plus minus} 67 pM and a receptor density (Bmax) value of 36.4 {plus minus} 2.7 fmol/mg protein. The high affinity of this site for delta opioid receptor ligands and its low affinity for mu or kappa receptor-selective ligands are consistent with its being a delta opioid receptor. The distribution of these sites in rat brain, observed by receptor autoradiography, is also consistent with that of delta opioid receptors. Association and dissociation binding kinetics of 1.0 nM (125I) DPDPE are monophasic at 25 degrees C. The association rate (k + 1 = 5.80 {plus minus} 0.88 {times} 10(7) M-1 min-1) is about 20- and 7-fold greater than that measured for 1.0 nM (3H) DPDPE and 0.8 nM (3H) (D-Pen2,4{prime}-Cl-Phe4, D-Pen5)enkephalin, respectively. The dissociation rate of (125I)DPDPE (0.917 {plus minus} 0.117 {times} 10(-2) min-1) measured at 1.0 nM is about 3-fold faster than is observed for either of the other DPDPE analogs. The rapidmore » binding kinetics of (125I)DPDPE is advantageous because binding equilibrium is achieved with much shorter incubation times than are required for other cyclic enkephalin analogs. This, in addition to its much higher specific activity, makes (125I)DPDPE a valuable new radioligand for studies of delta opioid receptors.« less

Authors:
; ; ; ; ; ; ; ; ;  [1]
  1. Department of Pharmacology, University of Arizona, College of Medicine, Tucson (United States)
Publication Date:
OSTI Identifier:
6144464
Resource Type:
Journal Article
Journal Name:
Journal of Pharmacology and Experimental Therapeutics; (United States)
Additional Journal Information:
Journal Volume: 258:3; Journal ID: ISSN 0022-3565
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ENDORPHINS; RECEPTORS; ENKEPHALINS; BIOCHEMICAL REACTION KINETICS; AFFINITY; AUTORADIOGRAPHY; BRAIN; CELL MEMBRANES; COMPARATIVE EVALUATIONS; LIGANDS; RATS; TRITIUM COMPOUNDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; CELL CONSTITUENTS; CENTRAL NERVOUS SYSTEM; DRUGS; EVALUATION; HYDROGEN COMPOUNDS; KINETICS; MAMMALS; MEMBRANE PROTEINS; MEMBRANES; NERVOUS SYSTEM; NEUROREGULATORS; ORGANIC COMPOUNDS; ORGANS; PEPTIDES; POLYPEPTIDES; PROTEINS; REACTION KINETICS; RODENTS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Knapp, R J, Sharma, S D, Toth, G, Duong, M T, Fang, L, Bogert, C L, Weber, S J, Hunt, M, Davis, T P, and Wamsley, J K. (D-Pen2,4 prime -125I-Phe4,D-Pen5)enkephalin: A selective high affinity radioligand for delta opioid receptors with exceptional specific activity. United States: N. p., 1991. Web.
Knapp, R J, Sharma, S D, Toth, G, Duong, M T, Fang, L, Bogert, C L, Weber, S J, Hunt, M, Davis, T P, & Wamsley, J K. (D-Pen2,4 prime -125I-Phe4,D-Pen5)enkephalin: A selective high affinity radioligand for delta opioid receptors with exceptional specific activity. United States.
Knapp, R J, Sharma, S D, Toth, G, Duong, M T, Fang, L, Bogert, C L, Weber, S J, Hunt, M, Davis, T P, and Wamsley, J K. 1991. "(D-Pen2,4 prime -125I-Phe4,D-Pen5)enkephalin: A selective high affinity radioligand for delta opioid receptors with exceptional specific activity". United States.
@article{osti_6144464,
title = {(D-Pen2,4 prime -125I-Phe4,D-Pen5)enkephalin: A selective high affinity radioligand for delta opioid receptors with exceptional specific activity},
author = {Knapp, R J and Sharma, S D and Toth, G and Duong, M T and Fang, L and Bogert, C L and Weber, S J and Hunt, M and Davis, T P and Wamsley, J K},
abstractNote = {(D-Pen2,4{prime}-125I-Phe4,D-Pen5)enkephalin ((125I)DPDPE) is a highly selective radioligand for the delta opioid receptor with a specific activity (2200 Ci/mmol) that is over 50-fold greater than that of tritium-labeled DPDPE analogs. (125I)DPDPE binds to a single site in rat brain membranes with an equilibrium dissociation constant (Kd) value of 421 {plus minus} 67 pM and a receptor density (Bmax) value of 36.4 {plus minus} 2.7 fmol/mg protein. The high affinity of this site for delta opioid receptor ligands and its low affinity for mu or kappa receptor-selective ligands are consistent with its being a delta opioid receptor. The distribution of these sites in rat brain, observed by receptor autoradiography, is also consistent with that of delta opioid receptors. Association and dissociation binding kinetics of 1.0 nM (125I) DPDPE are monophasic at 25 degrees C. The association rate (k + 1 = 5.80 {plus minus} 0.88 {times} 10(7) M-1 min-1) is about 20- and 7-fold greater than that measured for 1.0 nM (3H) DPDPE and 0.8 nM (3H) (D-Pen2,4{prime}-Cl-Phe4, D-Pen5)enkephalin, respectively. The dissociation rate of (125I)DPDPE (0.917 {plus minus} 0.117 {times} 10(-2) min-1) measured at 1.0 nM is about 3-fold faster than is observed for either of the other DPDPE analogs. The rapid binding kinetics of (125I)DPDPE is advantageous because binding equilibrium is achieved with much shorter incubation times than are required for other cyclic enkephalin analogs. This, in addition to its much higher specific activity, makes (125I)DPDPE a valuable new radioligand for studies of delta opioid receptors.},
doi = {},
url = {https://www.osti.gov/biblio/6144464}, journal = {Journal of Pharmacology and Experimental Therapeutics; (United States)},
issn = {0022-3565},
number = ,
volume = 258:3,
place = {United States},
year = {Sun Sep 01 00:00:00 EDT 1991},
month = {Sun Sep 01 00:00:00 EDT 1991}
}