TY - JOUR
T1 - Antinociceptive effects of [D-Ala2]deltorphin II, a highly selective δ agonist in vivo
AU - Jiang, Qi
AU - Mosberg, Henry I.
AU - Porreca, Frank
N1 - Funding Information:
Supported by USPHS Grants DA 04285, DA 06284 and DA 03910 from the National Institute on Drug Abuse. H.I.M. is the recipient of a Research Scientist Development Award (DA 00118).
PY - 1990
Y1 - 1990
N2 - The present study has characterized the antinociceptive actions of [D-Ala2]deltorphin II following intracerebroventricular (i.c.v.) administration in the mouse tail-flick test. [D-Ala2]deltorphin II produced dose- and time-related antinociception, with maximal effects at +10 min and significant antinociception which lasted for 40-60 min. [D-Ala2]deltorphin II was 13-fold more potent than i.c.v. [D-Pen2, D-Pen5]enkephalin (DPDPE), a second highly selective δ agonist, and approximately equipotent with i.c.v. morphine in producing antinociception. The antinociceptive effects of i.c.v. [D-Ala2]deltorphin II and DPDPE, but not those of morphine, were antagonized by the selective δ antagonist, ICI 174,864. In contrast, pretreatment with the non-equilibrium μ antagonist, β-funaltrexamine blocked morphine antinociception, but failed to antagonize [D-Ala2]deltorphin II and DPDPE antinociception. These data indicate that [D-Ala2]deltorphin II produced its antinociceptive effects at a supraspinal δ receptor. [D-Ala2]deltorphin II appears to be the most appropriate δ opioid agonist currently available for studies in vivo and support the involvement of δ receptors in supraspinal antinociception.
AB - The present study has characterized the antinociceptive actions of [D-Ala2]deltorphin II following intracerebroventricular (i.c.v.) administration in the mouse tail-flick test. [D-Ala2]deltorphin II produced dose- and time-related antinociception, with maximal effects at +10 min and significant antinociception which lasted for 40-60 min. [D-Ala2]deltorphin II was 13-fold more potent than i.c.v. [D-Pen2, D-Pen5]enkephalin (DPDPE), a second highly selective δ agonist, and approximately equipotent with i.c.v. morphine in producing antinociception. The antinociceptive effects of i.c.v. [D-Ala2]deltorphin II and DPDPE, but not those of morphine, were antagonized by the selective δ antagonist, ICI 174,864. In contrast, pretreatment with the non-equilibrium μ antagonist, β-funaltrexamine blocked morphine antinociception, but failed to antagonize [D-Ala2]deltorphin II and DPDPE antinociception. These data indicate that [D-Ala2]deltorphin II produced its antinociceptive effects at a supraspinal δ receptor. [D-Ala2]deltorphin II appears to be the most appropriate δ opioid agonist currently available for studies in vivo and support the involvement of δ receptors in supraspinal antinociception.
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U2 - 10.1016/0024-3205(90)90545-3
DO - 10.1016/0024-3205(90)90545-3
M3 - Article
C2 - 2170791
AN - SCOPUS:0025151599
SN - 0024-3205
VL - 47
SP - PL43-PL47
JO - Life Sciences
JF - Life Sciences
IS - 11
ER -