CLONING AND CHARACTERIZATION OF A TRUNCATED DOPAMINE D1 RECEPTOR FROMGOLDFISH RETINA - STIMULATION OF CYCLIC-AMP PRODUCTION AND CALCIUM MOBILIZATION

Receptors for dopamine are present on horizontal cells of fish retina that are linked to the activation of adenylate cyclase. In the present study, the goldfish (Carassius auratus) gene that encodes these recep tors, referred to as gfD1, was isolated and analyzed. A single open re ading frame within the gfD1 gene encodes a protein of 363 amino acids that is highly homologous with dopamine D1 receptors from rats and hum ans. Interestingly, the carboxyl terminus of gfD1 lacks 80 amino acids that are present in the mammalian receptor sequences. RNA analysis us ing the polymerase chain reaction demonstrated that the gene is expres sed in the goldfish retina and is intronless within the coding region. The fact that gfD1 encodes a dopamine D1 receptor was demonstrated th rough pharmacological analysis of transfected cells. Both the gfD1 rec eptor and the human D1 receptor expressed in mammalian cells had high affinity for SCH-23390 and other D1-specific ligands. In addition, the gfD1 receptor and the human D1 receptor were able to stimulate the ac cumulation of cAMP in response to SKF-38393 or dopamine. Interestingly , stimulation of both the gfD1 and human receptors with dopamine also resulted in an increase in intracellular Ca2+. Finally, long term pret reatment of transfected cells with dopamine resulted in the desensitiz ation and down-regulation of both the goldfish and human receptors.