The effects of long-term treatment of NG108-15 cells with penta- and tetrapeptide enkephalin dimers on opioid receptor binding and cyclic AMP (cAMP) levels.
1. The effects of chronic treatment with a dimeric or monomeric penta- or tetrapeptide enkephalin analogue on binding and cyclic AMP (cAMP) accumulation in NG108-15 cells have been studied. 2. When the cells were cultured in the presence of 1 mumol of a pentapeptide analogue (dimer or monomer) for up to 96 hr, binding was reduced by greater than or equal to 90%. 3. In contrast, in the presence of 1 mumol of a tetrapeptide analogue (dimer or monomer), binding was reduced by only less than or equal to 30%. 4. The analogues had varying effects on regulation of cAMP formation. Desensitization, indicated by impaired opioid-mediated inhibition of prostaglandin E1 (PGE1)-stimulated cAMP accumulation, was clearly apparent only for cells pretreated with [D-Ala2,D-Leu5]enkephalin (DADLE), while cells pretreated with [D-Ala2,Leu5-NH-CH2-]2 (DPE2) showed minor impairment. 5. Thus, ligand dimerization appeared to have a modulating effect on regulation of adenylate cyclase activity but not to affect opioid-induced down-regulation.
Krumins
S A
SA
Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, Bethesda, Maryland 20205.
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004745:Enkephalins / Q000494:pharmacology*; D005910:Glioma; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004745:Enkephalins; D011957:Receptors, Opioid; D000242:Cyclic AMP; D000527:Alprostadil