Dopamine receptors in a human colonic cancer cell line (HT29). Some receptor-related biological effects of dopamine
✍ Scribed by J. L. Scemama; C. Ruellan; P. Clerc; F. Clemente; A. Ribet
- Publisher
- John Wiley and Sons
- Year
- 1984
- Tongue
- French
- Weight
- 482 KB
- Volume
- 34
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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 t o evaluate the effect of dopamine on CAMP, protein and DNA synthesis. The binding characteristics of 'H-dopamine on the tumor cells were rapid, reversible, specific, saturable and stereospecific. The first site characterized corresponds to a D, subtype: K, 3.09 nM.
insensitive to sulpiride, unrelated t o adenylate cyclase. Competitive inhibitions of 'H-dopamine binding by different drugs showed the existenceof asecond bindingsite, D,, with an apparent affinity for dopamine of 6,700 nn. The rank order of potency of inhibitors of 'H-dopamine binding was: haloperidol > dopamine > cis flupenthixol > (+) butaclamol > (-) butaclamol > trans flupenthixol > isoproterenol > clonidine > prazosin. D, binding sites are modulated with age, Bmax was I16 fmol/106 cells on the 5th day and decreased to 8.2 fmol/106 cells on the 15th day of culture. Cell culture in serum-deprived medium allowed an increase in the number of high-affinity receptor sites. D, sites are coupled to adenylate cyclase as shown by a dosedependent cAMP accumulation from lod M to loJ M dopamine concentrations. Interacting with D, sites, dopamine evokes an increase in protein synthesis with no modification of ' H 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.