Comparative effects of dynorphin A(1-9) pyrrolidine analogs on isolated tissues.
Three dynorphin A(1-9) pyrrolidine analogs were synthesized by substituting isoleucine at position 8 with alanine (Ala), D-alanine (D-ala), and D-leucine (D-leu), and assayed for their effect on electrically induced twitches of the isolated guinea pig ileum and mouse vas deferens. All three dynorphin A(1-9) pyrrolidine analogs caused inhibition of the evoked twitches of the two preparations dose-dependently that was reversed by naloxone. However, the substitution by alanine or D-alanine resulted in a decrease in potency on guinea pig ileum when compared to dynorphin A(1-9) pyrrolidine and substitution by D-leucine caused a considerable loss of potency in both mouse vas deferens and guinea pig ileum. Although these substitutions reduced overall potency, a change of potency ratio towards more delta selectivity resulted.
D000818:Animals; D004399:Dynorphins / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000502:physiology
D011759:Pyrrolidines; D004399:Dynorphins