TY - JOUR
T1 - δ-Opioid receptor agonists produce antinociception and [35S]GTPγS binding in μ receptor knockout mice
AU - Hosohata, Yoshiaki
AU - Vanderah, Todd W.
AU - Burkey, Thomas H.
AU - Ossipov, Michael H.
AU - Kovelowski, Carl J.
AU - Sora, Ichiro
AU - Uhl, George R.
AU - Zhang, Xiaoyan
AU - Rice, Kenner C.
AU - Roeske, William R.
AU - Hruby, Victor J.
AU - Yamamura, Henry I.
AU - Lai, Josephine
AU - Porreca, Frank
PY - 2000/2/4
Y1 - 2000/2/4
N2 - We examined the effects of [D-Pen2,D-Pen5]enkephalin (DPDPE), [D- Ala2,Glu4]deltorphin (DELT), and (+)-4-[(αR)-α((2S,5R)-4-Allyl-2,5- dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) on [35S]GTPγS binding in brain membranes prepared from μ-opioid receptor knockout (-/-) mice. The potency and maximal response (E(max)) of these agonists were unchanged compared to control mice. In contrast, while the potency of [D-Pen2,pCl-Phe4,D-Pen5]enkephalin (pCl-DPDPE) was not significantly different, the E(max) was reduced as compared to controls. In the tail-flick test, intracerebroventricular (i.c.v.) or intrathecal (i.th.) DELT produced antinociceptive effects in -/- mice with potency that did not differ significantly from controls. In contrast, the antinociceptive potency of i.c.v. and i.th. DPDPE was displaced to the right by 4- and 9-fold in -/- compared to control mice, respectively. Reduced DPDPE antinociceptive potency in -/- mice, taken together with reduced DPDPE- and pCl-DPDPE- stimulated G protein activity in membranes prepared from -/- mice, demonstrate that these agonists require μ-opioid receptors for full activity. However, because DELT mediated G protein activation and antinociception were both comparable between -/- and wild type mice, we conclude that the μ-opioid receptor is not a critical component of δ-opioid receptor function. (C) 2000 Elsevier Science B.V.
AB - We examined the effects of [D-Pen2,D-Pen5]enkephalin (DPDPE), [D- Ala2,Glu4]deltorphin (DELT), and (+)-4-[(αR)-α((2S,5R)-4-Allyl-2,5- dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) on [35S]GTPγS binding in brain membranes prepared from μ-opioid receptor knockout (-/-) mice. The potency and maximal response (E(max)) of these agonists were unchanged compared to control mice. In contrast, while the potency of [D-Pen2,pCl-Phe4,D-Pen5]enkephalin (pCl-DPDPE) was not significantly different, the E(max) was reduced as compared to controls. In the tail-flick test, intracerebroventricular (i.c.v.) or intrathecal (i.th.) DELT produced antinociceptive effects in -/- mice with potency that did not differ significantly from controls. In contrast, the antinociceptive potency of i.c.v. and i.th. DPDPE was displaced to the right by 4- and 9-fold in -/- compared to control mice, respectively. Reduced DPDPE antinociceptive potency in -/- mice, taken together with reduced DPDPE- and pCl-DPDPE- stimulated G protein activity in membranes prepared from -/- mice, demonstrate that these agonists require μ-opioid receptors for full activity. However, because DELT mediated G protein activation and antinociception were both comparable between -/- and wild type mice, we conclude that the μ-opioid receptor is not a critical component of δ-opioid receptor function. (C) 2000 Elsevier Science B.V.
KW - δ-Opioid receptor
KW - μ-Opioid receptor
KW - μ-Opioid receptor-knockout mice
KW - Antinociception
KW - G protein
KW - Opioid drug
UR - http://www.scopus.com/inward/record.url?scp=0033962799&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033962799&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(99)00897-3
DO - 10.1016/S0014-2999(99)00897-3
M3 - Article
C2 - 10675732
AN - SCOPUS:0033962799
SN - 0014-2999
VL - 388
SP - 241
EP - 248
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -