Abstract
In rat brain membrane preparations, the parenterally and orally active peptide, [D-Ala2, MePhe4, Met(O)5-ol]-enkephalin, binds to morphine receptor sites ([3H]naloxone or [3H]dihydromorphine binding sites) with an affinity higher than that for enkephalin receptor sites ([125I] [D-Ala2, D-Leu5]-enkephalin binding sites). [125I] [D-Ala2, MePhe4, Met(O)5-ol]-enkephalin binds to morphine receptor sites stereospecifically, in a saturable manner and with characteristics similar to that of [3H]dihydromorphine; this ligand can be used as an 125I-labeled probe to measure specific binding to morphine receptor sites. Na+ decreases and Mn2+ increases the binding capacity with a concomitant reduction of affinity for [125I] [D-Ala2, MePhe4, Met(O)5-ol]-enkephalin. This peptide does not bind to neuroblastoma cells with high affinity. The brain regional distribution of binding of [125I] [D-Ala2, MePhe4, Met(O)5-ol]-enkephalin or [3H]naloxone and [125I] [D-Ala2, D-Leu5]-enkephalin are different. The differential potency of binding of opiate agonists, antagonists, mixed agonist-antagonists, enkephalins and enkephalin analogues is studied by competition of binding of [3H]naloxone or [125I] [D-Ala2, MePhe4, Met(O)5-ol]-enkephalin (morphine receptor) and of [125I] [D-Ala2, D-Leu5]-enkephalin sites (enkephalin receptor). All of these results support the contention that there are multiple opiate receptors with differing characteristics.
ACKNOWLEDGMENT We are grateful to Mark Collins for excellent technical assistance.
- Copyright © 1979 by Academic Press, Inc.
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|