Anti-DRD5 (aa 1-155) polyclonal antibody

Dopamine agonists such as bromocriptine and cabergoline have been successfully used in the treatment of pituitary prolactinomas and other neuroendocrine tumors. However, their therapeutic mechanisms are not fully understood. In this study we demonstrated that DRD5 (dopamine receptor D5) agonists were potent inhibitors of pituitary tumor growth. We further found that DRD5 activation increased production of reactive oxygen species (ROS), inhibited the MTOR pathway, induced macroautophagy/autophagy, and led to autophagic cell death (ACD) in vitro and in vivo. In addition, DRD5 protein was highly expressed in the majority of human pituitary adenomas, and treatment of different human pituitary tumor cell cultures with the DRD5 agonist SKF83959 resulted in growth suppression, and the efficacy was correlated with the expression levels of DRD5 in the tumors. Furthermore, we found that DRD5 was expressed in other human cancer cells such as glioblastomas, colon cancer, and gastric cancer. DRD5 activation in these cell lines suppressed their growth, inhibited MTOR activity, and induced autophagy. Finally, in vivo SKF83959 also inhibited human gastric cancer cell growth in nude mice. Our studies revealed novel mechanisms for the tumor suppressive effects of DRD5 agonists, and suggested a potential use of DRD5 agonists as a novel therapeutic approach in the treatment of different human tumors and cancers.

Objective: The authors investigated the possibility that genetic variation or mutation of the dopamine D-5 receptor gene might modify susceptibility to schizophrenia. Method: Twenty-three Icelandic and English pedigrees containing multiple cases of schizophrenia were genotyped by using a highly informative microsatellite for the D-5 dopamine receptor gene DRD5. Results: By means of three different affection models, negative lod scores were obtained under assumptions of autosomal dominant and recessive inheritance. There was no evidence for locus heterogeneity. Nonparametric extended relative pair analysis also produced negative results. Conclusions: These data indicate that mutations of the D-5 dopamine receptor gene ave not a major cause of schizophrenia in these pedigrees. Because of the probable existence of locus heterogeneity, the D-5 receptor gene may be of etiologic importance in other families with schizophrenia.