Potent cyclic enkephalin analogues for delta opioid receptors in the rat brain

Conference · Sat Mar 01 00:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5278567

Lui, G; Kao, J; Hruby, V; Morelli, M; Gulya, K; Yamamura, H I

(/sup 3/H) (D-Pen/sup 2/,D-Pen/sup 5/) enkephalin ((/sup 3/H)DPDPE) and (/sup 3/H) (D-Pen/sup 2/, L-Pen/sup 5/) enkephalin ((/sup 3/H)DPLPE) characterization studies showed high affinity binding of these radioligands to rat brain membranes with dissociation constants of 1.8 and 1.0 nM, respectively, while a similar number of receptor density was found with both radiolabeled ligands (77 fmoles/mg protein). Unlabeled DPDPE inhibited both radioligands with high affinity (IC50 = 7 nM0 while morphine (IC50 = 80 nM), DAGO (IC50 = 250 nM) and PLO17 (no inhibition at 1000 nM) were less effective in inhibiting the binding, thus, illustrating the selective action of these radiolabeled ligands at the delta opioid receptor. A series of conformationally restricted D-penicillamine containing cyclic enkephalin analogues were synthesized using standard solid phase methods and their ability to inhibit (/sup 3/H)DPDPE and (/sup 3/H)DPLPE were examined in rat brain radioreceptor assays. Substitutions in the DPDPE molecule were made in phe/sup 4/. These substitutions were pNO/sub 2/-phe/sup 4/, beta-methyl-phe/sup 4/, pNO/sub 2/-beta-methyl-phe/sub 4/, pNO/sub 2/-beta-methyl-phe/sup 4/ (three isomeric forms: A,B,D). The IC50 values for the above enkephalin analogues were 3.7, 16, 7, 7, 200 nM, respectively. Thus, these potent analogues of DPDPE should be useful in determining the structure activity relationships of the delta opioid receptor in rat brain.

• Research Organization: Univ. of Arizona, Tucson
• OSTI ID: 5278567
• Report Number(s): CONF-8604222-; TRN: 86-030429
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ENKEPHALINS
BIOCHEMICAL REACTION KINETICS
MORPHINE
RECEPTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
AFFINITY
BRAIN
CELL MEMBRANES
LIGANDS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALOIDS
ANALGESICS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ENDORPHINS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NARCOTICS
NERVOUS SYSTEM
NEUROREGULATORS
OPIUM
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PROTEINS
REACTION KINETICS
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques