Browsing by Author "CHOH, HL"

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    LACK OF MIXED AGONIST-ANTAGONIST PROPERTIES OF [GLN8-GLY31]-BETA-H-EP-GLY-GLY-NH2 AND [ARG9,19,24,28,29]-BETA-H-EP IN THE RAT VAS-DEFERENS NEUROEFFECTOR JUNCTION - STUDIES WITH NALOXONE, BETA-FUNALTREXAMINE AND ICI-174,864
    (1989) VALENZUELA, R; CHOH, HL; HUIDOBROTORO, JP
    The 1-27 truncated fragment of .beta.h-endorphin (.beta.h-EP) as well as [Gln8,Gly31]-.beta.h-EP-Gly-Gly-NH2 or [Arg9,19,24,28,29]-.beta.h-EP exhibited opiate agonist activity in the rat vas deferens bioassay; the potency of these peptides was 3 to 6 times less than that of .beta.h-EP. None of these compounds exhibited any degree of antagonism towards the inhibitory action of .beta.h-EP. Naloxone antagonized and reversed the inhibitory action of .beta.h-EP and its analogues though with varying potencies. The apparent naloxone-pA2 value for .beta.h-EP was 8.94; that for [Gln8-Gly31]-.beta.h-EP-Gly-Gly-NH2 was 8.08 and that for [Arg9,19,24,28,29]-.beta.h-EP was 8.38. .beta.-Funaltrexamine (.beta.-FNA) potently antagonized the inhibitory action of .beta.h-EP following non-equilibrium kinetics. Tissue preincubation with 10 nM .beta.-FNA for 60 min followed by extensive washing caused a 10-fold increase in the .beta.h-EP IC50. However, 10 nM .beta.-FNA caused only a 1.2 increase in the IC50 of [Gln8 Gly31]-.beta.h-EP-Gly-Gly-NH2 and a 4.1-fold increase in the IC50 of [Arg9,19,24,28,29]-.beta.h-EP. In contrast, preincubation of the tissue with 3 .mu.M ICI 174,864 did not modify the potency of .beta.h-EP or its structural analogues. However, a 60 min pretreatment with 10 .mu.M .beta.-FNA followed by the addition of 3 .mu.M ICI 174,864 revealed a further decrease in the potency of the opiopeptins compared with tissues exposed to .beta.-FNA alone or ICI 174,864 alone. In conclusion, the inhibitory action of these peptides is remarkably sensitive to .beta.-FNA antagonism; in addition the peptides act as pure opiate agonists in marked contrast with the agonist-antagonist properties described in the CNS.