Abstract
Agonist, and antagonist effects of the proposed kappa opioid agonist, U50,488H (U50) have been studied in an experimental model of seizure activity (flurothyl-induced seizure threshold) (ST) and in the central modulation of spontaneous, volume-induced micturition contractions (bladder motility) (BM) in rats. Intracerebroventricular (i.c.v.) administration of U50 (at the doses tested) did not produce any agonist effect in either ST or in BM. In contrast, i.c.v. administration of [D-Ala2, NMPhe4, Gly-o1]enkephalin (DAGO) or etorphine, agonists with activity at mu opioid receptors, produced an elevation of ST and inhibition of BM. The elevation in ST produced by etorphine (0.004 nmol) was prevented by prior treatment with U50. In contrast, the approximately equieffective elevation in ST resulting from DAGO was not affected by U50 pretreatment. Similarly, pretreatment of rats with U50 antagonized the approximately equieffective BM effects of etorphine, but not those of DAGO. As both DAGO and etorphine are thought to exert their effects via the opiate mu receptor, the results may be consistent with the view that subpopulations of mu receptors exist within the central nervous system; these sites may be differentially associated with the kappa receptor.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2511-2516 |
| Number of pages | 6 |
| Journal | Life Sciences |
| Volume | 41 |
| Issue number | 23 |
| DOIs | |
| State | Published - Dec 7 1987 |
Fingerprint
ASJC Scopus subject areas
- Pharmacology
Cite this
Differential antagonism of mu agonists by U50,488H in the rat. / Porreca, Frank; Tortella, Frank C.
In: Life Sciences, Vol. 41, No. 23, 07.12.1987, p. 2511-2516.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential antagonism of mu agonists by U50,488H in the rat
AU - Porreca, Frank
AU - Tortella, Frank C.
PY - 1987/12/7
Y1 - 1987/12/7
N2 - Agonist, and antagonist effects of the proposed kappa opioid agonist, U50,488H (U50) have been studied in an experimental model of seizure activity (flurothyl-induced seizure threshold) (ST) and in the central modulation of spontaneous, volume-induced micturition contractions (bladder motility) (BM) in rats. Intracerebroventricular (i.c.v.) administration of U50 (at the doses tested) did not produce any agonist effect in either ST or in BM. In contrast, i.c.v. administration of [D-Ala2, NMPhe4, Gly-o1]enkephalin (DAGO) or etorphine, agonists with activity at mu opioid receptors, produced an elevation of ST and inhibition of BM. The elevation in ST produced by etorphine (0.004 nmol) was prevented by prior treatment with U50. In contrast, the approximately equieffective elevation in ST resulting from DAGO was not affected by U50 pretreatment. Similarly, pretreatment of rats with U50 antagonized the approximately equieffective BM effects of etorphine, but not those of DAGO. As both DAGO and etorphine are thought to exert their effects via the opiate mu receptor, the results may be consistent with the view that subpopulations of mu receptors exist within the central nervous system; these sites may be differentially associated with the kappa receptor.
AB - Agonist, and antagonist effects of the proposed kappa opioid agonist, U50,488H (U50) have been studied in an experimental model of seizure activity (flurothyl-induced seizure threshold) (ST) and in the central modulation of spontaneous, volume-induced micturition contractions (bladder motility) (BM) in rats. Intracerebroventricular (i.c.v.) administration of U50 (at the doses tested) did not produce any agonist effect in either ST or in BM. In contrast, i.c.v. administration of [D-Ala2, NMPhe4, Gly-o1]enkephalin (DAGO) or etorphine, agonists with activity at mu opioid receptors, produced an elevation of ST and inhibition of BM. The elevation in ST produced by etorphine (0.004 nmol) was prevented by prior treatment with U50. In contrast, the approximately equieffective elevation in ST resulting from DAGO was not affected by U50 pretreatment. Similarly, pretreatment of rats with U50 antagonized the approximately equieffective BM effects of etorphine, but not those of DAGO. As both DAGO and etorphine are thought to exert their effects via the opiate mu receptor, the results may be consistent with the view that subpopulations of mu receptors exist within the central nervous system; these sites may be differentially associated with the kappa receptor.
UR - http://www.scopus.com/inward/record.url?scp=0023622773&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023622773&partnerID=8YFLogxK
U2 - 10.1016/0024-3205(87)90435-8
DO - 10.1016/0024-3205(87)90435-8
M3 - Article
C2 - 2824958
AN - SCOPUS:0023622773
VL - 41
SP - 2511
EP - 2516
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 23
ER -