delta EPhe4-enkephalin analogs. Delta receptors in rat brain are different from those in mouse vas deferens.
Conformationally restricted enkephalin analogs containing E-cyclopropylphenylalanine (delta EPhe), [D-Ala2, (2R,3S)-delta EPhe4,Leu5]enkephalin and its (2S,3R) isomer, were evaluated in receptor-binding assays using rat brain and in assays using muscle preparations. The (2S,3R) isomer was almost completely inactive in all assays. In contrast, the (2R,3S) isomer showed a very high affinity for the delta and a very weak affinity for the mu receptors in rat brain. The extent of delta affinity and the selectivity of this isomer were almost equal to those of [D-Pen2,D-Pen5]enkephalin. However, the (2R,3S) isomer was inactive in both the mouse vas deferens and guinea pig ileum assays, and showed no antagonistic activity in these tissues. These results indicate that the (2R,3S) isomer interacts with the delta receptors in rat brain, but not with those in the mouse vas deferens, and they suggest that the delta receptors in the central and peripheral nervous systems are different from each other.
Shimohigashi
Y
Y
Laboratory of Biochemistry, Faculty of Science, Kyushu University, Fukuoka, Japan.
Costa
T
T
Pfeiffer
A
A
Herz
A
A
Kimura
H
H
Stammer
C H
CH
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine / Q000031:analogs & derivatives; D004745:Enkephalins / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007536:Isomerism; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D014649:Vas Deferens / Q000378:metabolism*
D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C053829:enkephalin-Leu, Ala(2)-(cyclopropyl-Phe)(4)-