Differential effects of opioid and adrenergic agonists on proliferation in a cultured cell line.
A novel clonal cell line transfected with the delta-opioid receptor (delta-OR) encoding gene was used to study agonist-activated regulation of cell proliferation. In this cell line, endogenous beta2-adrenergic receptors (beta2-ARs) are coexpressed with the exogenous delta-ORs. Upon individual acute treatments with morphine and procaterol (a selective beta2-AR agonist), both the delta-OR and beta2-AR are coupled to differential modulation of cyclic AMP (cAMP) levels in accord with the classical second messenger response patterns to these agonists in the normal cellular settings of the receptors. But chronic morphine activation of the delta-OR inhibits cellular proliferation, while chronic procaterol activation of the beta2-AR stimulates it. Chronic treatment with the individual agonists is accompanied by differential activation of the mitogen-activated protein kinase (MAPK) isozymes, extracellular-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The findings suggest that chronic beta2-AR activation stimulates proliferation by interacting with the ERK signalling cascade independent of a cAMP-mediated pathway. In contrast to treatment with individual agonists, chronic dual agonist treatment suppresses procaterol-induced stimulation of ERK activity and stimulation of proliferation indicating that a cross-regulatory interaction occurs between the delta-OR and beta2-AR signalling systems in the cells under these conditions.
Agarwal
D
D
Cellular and Molecular Medicine, University of California San Diego Cancer Center, La Jolla, USA.
Glasel
J A
JA
D016475:3T3 Cells / Q000166:cytology / Q000201:enzymology; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D017265:Procaterol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000235:genetics*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D014316:Tritium
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000701:Analgesics, Opioid; D007004:Hypoglycemic Agents; D007328:Insulin; D011412:Propanolamines; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D017465:Receptors, Opioid, delta; D014316:Tritium; D005576:Colforsin; C026777:ICI 118551; D009020:Morphine; D000242:Cyclic AMP; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C033394:CGP 12177; D017265:Procaterol