Premium
Irreversible Activation of the Opiate Receptor of Neuroblastoma × Glioma Hybrid Cells by an Alkylating Benzomorphan Derivative
Author(s) -
Hallermayer Klaus,
Harmening Christine,
Merz Herbert,
Hamprecht Bernd
Publication year - 1983
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1983.tb00891.x
Subject(s) - neuroblastoma , glioma , derivative (finance) , opiate , cancer research , receptor , chemistry , neuroscience , biology , medicine , biochemistry , genetics , cell culture , financial economics , economics
The benozomorphan derivative (‐) ‐ 2 ‐[2 ‐ ( p ‐ bromoacetamidophenyl)ethyl] ‐ 5,9α ‐ dimethyl ‐ 2’‐ hydroxy ‐ 6,7 ‐ benzomorphan (BAB), capable of reacting with nucleophilic groups, acts on neuroblastoma × glioma hybrid cells as a potent, irreversible opiate agonist. Its potency in inhibiting the increase in cellular cyclic AMP, evoked by prostaglandin E 1 , is comparable to that of Leu‐enkephalin. This also applies to its capacity to compete with [ 3 H]d ‐ Ala 2 ‐ Met ‐ enkephalinamide ([ 3 H]DAEA) in binding on cell membrane preparations. The comparatively lower potency of (‐) ‐ 2 ‐ [2 ‐ ( p ‐ acetamidophenyl) ‐ ethyl]‐5,9α ‐ dimethyl‐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 [ 3 H]DAEA increases with prolonged preincubation time, and (3) AB behaves as a reversible agonist.