The present study showed that the glucocorticoid/progesterone antagonists, 17 beta-hydroxy-1 1 beta-(4-dimethylamino-phenyl-1)-17-(prop-1-ynyl)estra-4,9-dien+ ++-3-one (RU486) and 17 beta-hydroxy-11 beta-(4-dimethylamino-phenyl-1)-17-(propan-3-ol)estra-4,9-dien-3-o ne (ZK 98299), inhibit the binding of labeled dihydromorphine to mu-opioid receptors present on membrane preparations derived from rat and mouse brain, as well as from human neuroblastoma cells. The inhibitory effect of RU486 was dose-dependent and linked to a decrease of the affinity of labeled dihydromorphine to the mu-opioid receptors. Kinetic experiments have shown that RU486 induces a decrease of the association rate constant (k + 1) of dihydromorphine. RU486 also proved able to dissociate the dihydromorphine-mu-opioid receptor complex, although at a rate slower than that exhibited by unlabeled dihydromorphine. Finally, the addition of NaCl (100 mM) to the incubation buffer induced a 50% decrease of the inhibitory effect of RU486. A 6-day treatment of neuroblastoma cells with RU486 eliminated the inhibitory effect morphine exerts on the intracellular accumulation of cyclic AMP induced by prostaglandin E1. These results indicate that RU-486 may interact with brain mu-opioid receptors in vitro, by decreasing the affinity of opioid ligands.
Antiprogestins inhibit the binding of opioids to mu-opioid receptors in nervous membrane preparations / R. Maggi, F. Pimpinelli, L.A. Casulari, F. Piva, L. Martini. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - 301:1-3(1996 Apr 22), pp. 169-177.
|Titolo:||Antiprogestins inhibit the binding of opioids to mu-opioid receptors in nervous membrane preparations|
MAGGI, ROBERTO (Primo)
PIMPINELLI, FEDERICA ALBERTA ELENA MARIA (Secondo)
PIVA, FLAVIO (Penultimo)
MARTINI, LUCIANO (Ultimo)
|Parole Chiave:||Nervous system; Neuroblastoma; Opioid receptor; Steroid|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||22-apr-1996|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/0014-2999(96)00003-9|
|Appare nelle tipologie:||01 - Articolo su periodico|