Synergistic effects of neurotensin and beta-adrenergic agonist on 3,5-cyclic adenosine monophosphate accumulation and DNA synthesis in prostate cancer PC3 cells.
Since neurotensin is often co-stored with catecholamines and since it can excite the release of dopamine and norepinephrine, responses to this peptide might depend upon the activity of catecholaminergic systems. In this study, we used prostate cancer PC3 cells, which express neurotensin receptors and 12-adrenergic receptors, to demonstrate that neurotensin can potentiate the effects of isoproterenol on 3',5'-cyclic adenosine monophosphate (cAMP) formation and on inhibition of DNA synthesis. While neurotensin had only a slight effect on basal cAMP levels, it nearly doubled the response to isoproterenol even at maximal levels without altering potency. Neurotensin increased the rate of cAMP accumulation and the steady-state level achieved. Consistent with the known antimitogenic action of dibutyryl-cAMP in PC3 cells, isoproterenol was found to inhibit DNA synthesis concentration-dependently, measured using [3H]thymidine. Neurotensin enhanced DNA synthesis when given alone. However, it inhibited DNA synthesis when given with a threshold level of isoproterenol, which by itself had no significant effect. These results, demonstrating cross-talk in the neurotensin and beta-adrenergic signaling pathways, suggest that there may be other physiologic instances of similar interactions between neurotensin and catecholamines.
Mitra
S P
SP
Department of Physiology, University of Massachusetts Medical Center, Worcester 01655-0127, USA.
Carraway
R E
RE
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011471:Prostatic Neoplasms; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis; D018028:Receptors, Neurotensin / Q000096:biosynthesis; D013806:Theophylline / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000318:Adrenergic beta-Agonists; D010726:Phosphodiesterase Inhibitors; D011943:Receptors, Adrenergic, beta; D018028:Receptors, Neurotensin; D009496:Neurotensin; D003994:Bucladesine; D004247:DNA; D013806:Theophylline; D000242:Cyclic AMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine