Contributions of Conserved Serine Residues to the Interactions of Ligands with Dopamine D2 Receptors

• DOI: 10.1111/j.1471-4159.1992.tb09416.x
• Publication Date: 2006-10-06T03:12:11Z
• Authors: Barbara A. Cox; Robert A. Henningsen; Athena Spanoyannis; Rachael L. Neve; Kim A. Neve
• Keywords: Alanine; Radioligand; Endogenous agonist

Abstract: Four dopamine D2 receptor mutants were constructed, in each of which an alanine residue was substituted for one four conserved serine residues, i.e., Ser‐193, Ser‐194, Ser‐197, and Ser‐391. Wild‐type mutant receptors expressed transiently COS‐7 cells stably C6 glioma analysis ligand‐receptor interactions. In radioligand binding assays, the affinity decreased 50‐fold by substitution implicating this dopamine. Each had smaller decreases or more ligands tested, with no apparent relationship between class ligand pattern mutation‐induced changes affinity, except that potency agonists Ser‐193. The inhibition adenylyl cyclase reduced substantially Ser‐193 Ser‐197. Mutation Ser‐194 led to a complete loss efficacy p‐tyramine, would be consistent interaction p‐hydroxyl substituent is necessary activation occur. Because mutation corresponding residues β 2 ‐adrenergic has very different consequences, we conclude although position these highly among catecholamine receptors, as group are important agonists, function considered separately varies receptors.