Dopamine receptors in a human colonic cancer cell line (HT29). Some receptor-related biological effects of dopamine.
The presence of dopamine receptors in normal colonic cells has been postulated from physiological studies. The existence of such receptors in human colonic tumor cells and their role in tumor progression are still unknown. The aim of the present work was to characterize the dopaminergic receptors in a human colonic adenocarcinoma cell line (HT29) and to evaluate the effect of dopamine on cAMP, protein and DNA synthesis. The binding characteristics of 3H-dopamine on the tumor cells were rapid, reversible, specific, saturable and stereospecific. The first site characterized corresponds to a D3 subtype:KD 3.09 nM, insensitive to sulpiride, unrelated to adenylate cyclase. Competitive inhibitions of 3H-dopamine binding by different drugs showed the existence of a second binding site, D1, with an apparent affinity for dopamine of 6,700 nM. The rank order of potency of inhibitors of 3H-dopamine binding was: haloperidol greater than dopamine greater than cis flupenthixol greater than (+) butaclamol greater than (-) butaclamol greater than trans flupenthixol greater than isoproterenol greater than clonidine greater than prazosin. D3 binding sites are modulated with age, Bmax was 116 fmol/10(6) cells on the 5th day and decreased to 8.2 fmol/10(6) cells on the 15th day of culture. Cell culture in serum-deprived medium allowed an increase in the number of high-affinity receptor sites. D1 sites are coupled to adenylate cyclase as shown by a dose-dependent cAMP accumulation from 10(-8) M to 10(-5) M dopamine concentrations. Interacting with D1 sites, dopamine evokes an increase in protein synthesis with no modification of 3H thymidine incorporation. The present results indicate that the human colonic cancer cell line HT29 exhibits dopamine receptors and that stimulation may induce metabolic modifications in the tumor cells.
D001667:Binding, Competitive; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011954:Receptors, Dopamine / Q000378:metabolism*; D014316:Tritium
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011954:Receptors, Dopamine; D014316:Tritium; D000242:Cyclic AMP; D004298:Dopamine