Dopamine receptors in a human colonic cancer cell line (HT29). Some receptor‐related biological effects of dopamine

Abstract

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.

Dopamine functionalized polymeric nanoparticle for targeted drug delivery

“…Dopamine receptors positive human colon adenocarcinoma HT-29 cells has been used to investigate the dopamine receptors induced cellular uptake and normal mouse embryonic broblasts 3T3-L1 cells has been used as dopamine receptors negative control cells. 32,34 The drug encapsulated polymeric nanoparticle is incubated with cells for different time interval and then washed cells are imaged under uorescence microscope to observe the drug uptake using the uorescence property of drugs. Results show that uorescence of drugs is observed inside HT-29 cells indicating their internalization (Fig.…”

“…Although the exact reason of this subcellular targeting property needs further study, the tentative reasons of this targeting may be linked with the endocytosis pathway of polymeric nanoparticle via dopamine receptors. [32][33][34]…”

“…30 Thus dopamine functionalized nanocarriers have great advantage in the treatment of various neurodegenerative disorders. 31 In addition dopamine receptors are over expressed on certain cancer cells 32 and thus dopamine functionalized quantum dot has been used for specic targeting of cancer cells that have dopamine receptors. 33,34 Here we show that dopamine functionalized polymeric nanoparticle can selectively deliver anticancer drugs curcumin, camptothecin and doxorubicin to human colon adenocarcinoma cells and expected to be an alternative drug delivery carrier for in vitro and in vivo applications.…”

DRD2/DARPP‐32 Expression Correlates with Lymph Node Metastasis and Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma

“…Bromocriptine, a dopaminergic agonist, may mediate the growth-inhibitory effect of SCLC. 16 DRs expression have been found in many other malignant diseases, such as gastric cancer, 17 colon adenocarcinoma, 18,19 breast cancer, 20,21 gastrointestinal tumors, 22 melanoma, [23][24][25] adrenal tumors, 26 and pituitary tumors. 27 The purpose of this study was to clarify the association of DRD1 and DRD2 in esophageal squamous cell carcinoma (ESCC).…”