Dextrorphan Binds to Opioid Receptors in Guinea-Pig Brain Membranes And
Proc. Natl. Acad. Sci. USA Vol. 87, pp. 1629-1632, March 1990 Pharmacology Dextrorphan binds to opioid receptors in guinea-pig brain membranes and is an antagonist at opioid receptors in myenteric plexus (binding/guinea-pig ileum/levorphanol/stereoselectivity) AVRAM GOLDSTEIN AND ASHA NAIDU Department of Pharmacology, Stanford University, Stanford, CA 94305 Contributed by Avram Goldstein, December 11, 1989 ABSTRACT Dextrorphan (+)-tartrate, purified by re- LaRoche); [D-Ala,MePhe4,Gly-ol5]enkephalin (DAGO; Pe- peated crystallization to remove all traces of the enantiomer ninsula Laboratories) (2); trans-3,4-dichloro-N-methyl- levorphanol, binds to IL, 6, and K sites on guinea-pig brain N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide methane- membranes with lower affinities (by a factor of400-3200) than sulfonate (U50,488; Upjohn) (3); (-)-naloxone hydrochloride levorphanol. In the guinea-pig ileum myenteric plexus longi- (NAL; Endo Laboratories, New York); normorphine hydro- tudinal muscle preparation (GPI), dextrorphan, at 100-200 chloride (NOR) and (+)-naloxone hydrochloride (National ,uM, inhibits the electrically stimulated twitch, but this action Institute on Drug Abuse); N-methyl-D-aspartic acid (NMDA), is not blocked or reversed by naloxone; both (+)- and (-)- aminophosphonovalerate, norepinephrine (levarterenol), at- naloxone produce similar non-opioid twitch inhibition at com- ropine, and eserine (physostigmine) (Sigma). parable concentrations. At 10-20 jaM, dextrorphan' blocks and Preparation ofDEXp. [3H]LEV (Ro 1-5431/701, Hoffmann- reverses the twitch inhibition due to ,u and KWagonists, but the LaRoche; 17.4 Ci/mmol; 1 Ci = 37 GBq) was purified' by blockade can be overcome only partially by increasing the preparative reversed-phase HPLC (Waters, C18 AgBondaPak, agonist concentration.
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