Dopamine D1 receptors of the calf parathyroid gland: identification and characterization

HB Niznik, EL Fogel, CJ Chen, D Congo, EM Brown and P Seeman

Department of Medicine, University of Toronto, Ontario, Canada.

The dopamine D1 receptor was identified in the calf parathyroid gland. The binding of the selective D1 receptor antagonist [3H]SCH-23390 to membranes of calf parathyroid was specific, reversible, and saturable with a dissociation constant of approximately 200 pM and a receptor density of 30 fmol/mg of protein. Dopaminergic agonists and antagonists inhibited [3H]SCH-23390 binding in a concentration-dependent and stereoselective manner with an appropriate pharmacological specificity for D1 dopamine receptors. Moreover, potent dopaminergic agonists recognized two affinity forms of the receptor, one displaying high affinity for agonists, termed D1 High, and one with low affinity, D1 Low. The addition of the nonhydrolyzable guanine nucleotide guanyl 5'- yl-imidodiphosphate caused the complete transition of the agonist high affinity form (D1 High) of the receptor to one displaying only low affinity for agonists (D1 Low). Sodium ions, however, caused a approximately 5-fold decrease in the affinity of agonists at both D1 High and D1 Low. Virtually identical results were obtained on D1 receptor preparations of neural origin. The D1 receptor identified here appears to be the one responsible for the physiological effects on the parathyroid gland, because dopamine-stimulated cAMP accumulation is stereoselectively blocked by the D1 receptor antagonist SCH-23390 in dispersed cells of the parathyroid gland. Moreover, a series of nine dopaminergic antagonists and agonists shows an excellent correlation between their potency in [3H]SCH-23390 binding assays and their corresponding effects on cAMP accumulation. In the case of agonists, Ka for activation of cAMP accumulation agrees most closely with the agonist low affinity site in binding experiments. Specific [3H]spiperone binding to D2 dopamine receptors was not detected in this tissue and as such, the calf-parathyroid gland provides a model system in which to study the molecular characteristics of dopamine D1 receptor- mediated events.

Volume 34, Issue 1, pp. 29-36, 07/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics

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