Characterization of D1 dopamine receptors in the bovine pineal gland with [3H]SCH 23390.
Previous studies from this laboratory have shown that bovine pineal glands not only contain D2 dopamine receptors, but also that dopamine has dual effects on the activity of pineal serotonin N-acetyltransferase, inhibiting the basal activity at 0.1 microM and stimulating it at 10 microM. We report here that the bovine pineal gland also possesses D1 dopamine receptors, which were characterized by using [3H]SCH 23390, the selective D1 dopamine receptor antagonist. SCH 23390 bound to bovine pineal membranes in a stereoselective, saturable and reversible manner. The receptor density (Bmax) was 974 fmol/mg protein and the dissociation constant (KD), as determined by saturation studies, was 0.56 nM, which is in good agreement with the KD calculated from kinetic studies (0.40 nM). Dopaminergic receptor agonists and antagonists inhibited [3H]SCH 23390 binding in a concentration-dependent and stereoselective fashion, demonstrating a pharmacology characteristic of D1 dopamine receptors. On the other hand, serotonin and serotonin receptor antagonists had a very low potency in inhibiting [3H]SCH 23390 binding. Studies involving dopamine receptor agonists revealed a low density, high affinity binding site (10%) and a high density, low affinity binding site (90%) in the bovine pineal gland. The results of this study are interpreted to indicate that the effects of dopamine in the pineal gland are modulated through mechanisms that involve both D1 and D2 dopamine receptors.
Simonneaux
V
V
Department of Pharmacology, University of Nebraska College of Medicine, Omaha 68105.
Murrin
L C
LC
Ebadi
M
M
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001667:Binding, Competitive; D002417:Cattle; D018492:Dopamine Antagonists; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D010870:Pineal Gland / Q000032:analysis*; D011954:Receptors, Dopamine / Q000032:analysis* / Q000187:drug effects; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin / Q000032:analysis; D012701:Serotonin / Q000494:pharmacology; D013237:Stereoisomerism
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D012701:Serotonin; D006165:Guanylyl Imidodiphosphate