Irreversible activation of the opiate receptor of neuroblastoma X glioma hybrid cells by an alkylating benzomorphan derivative.

Abstract

The benozomorphan derivative (-)-2-[2-(p-bromoacetamidophenyl)ethyl]-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan (BAB), capable of reacting with nucleophilic groups, acts on neuroblastoma X glioma hybrid cells as a potent, irreversible opiate agonist. Its potency in inhibiting the increase in cellular cyclic AMP, evoked by prostaglandin E1, is comparable to that of Leu-enkephalin. This also applies to its capacity to compete with [3H]D-Ala2-Met-enkephalinamide ([3H]DAEA) in binding on cell membrane preparations. The comparatively lower potency of (-)-2-[2-(p-acetamidophenyl)-ethyl]-5,9 alpha-dimethly-2'-hydroxy-5,7-benzomorphan (AB), which differs from BAB in the substitution of the bromoacetamido group by an acetamido group, is of the same order of magnitude as that of morphine. The covalent interaction of BAB with the opiate receptors is deduced from the observations that (1) it is not possible to wash away this compound from the receptors, (2) the potency of BAB in inhibiting the specific binding of [3H]DAEA increases with prolonged preincubation time, and (3) AB behaves as a reversible agonist.

• Authors: K Hallermayer, C Harmening, H Merz, B Hamprecht
• Journal: Journal of neurochemistry (J Neurochem) Vol. 41 Issue 6 Pg. 1761-5 (Dec 1983) ISSN: 0022-3042 [Print] England
• PMID: 6315881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Affinity Labels
• Benzomorphans
• Morphinans
• Prostaglandins E
• Receptors, Opioid
• Enkephalin, Methionine
• enkephalinamide-Met, Ala(2)-
• 2-(2-(4-bromoacetamidophenyl)ethyl)-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan
• Cyclic AMP
• Alprostadil

Topics

• Affinity Labels
• Alprostadil
• Animals
• Benzomorphans (analogs & derivatives, pharmacology)
• Cells, Cultured
• Cyclic AMP (metabolism)
• Dose-Response Relationship, Drug
• Enkephalin, Methionine (analogs & derivatives, metabolism)
• Glioma
• Hybrid Cells (metabolism)
• Morphinans (pharmacology)
• Neuroblastoma
• Prostaglandins E (pharmacology)
• Receptors, Opioid (metabolism)