Browsing by Author "VALENZUELA, R"

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    E-2078, A POTENT, SELECTIVE AND STABLE DYNORPHIN ANALOG WITH PREFERENTIAL ACTIVITY FOR THE KAPPA-OPIOID RECEPTOR SUBTYPE ON THE MOUSE VAS-DEFERENS NEUROEFFECTOR JUNCTION
    (1991) VALENZUELA, R; TACHIBANA, S; HUIDOBROTORO, JP
    The profile of opioid activity of E-2078, a synthetic stable dynorphin analog, was examined in the mouse vas deferens bioassay and compared to that of methionine enkephalin and nonpeptide kappa agonists in the absence and in the presence of selective antagonists for the mu-, kappa- and delta-opioid receptor subtypes. The inhibitory action of E-2078 and related kappa agonists was specifically and potently antagonized only by norbinaltorphimine, revealing the presence of kappa receptors in this tissue and the predominant kappa activity of E-2078.
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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.