Constitutive activity of dopamine D1- receptor subtypes
Dopamine (DA) mediates brain functions through its interaction with membrane-bound receptors belonging to the superfamily of G-protein-coupled receptors. The DA receptors are divided into two groups: the D1 family (D(1A) and D(1B)/D5) and the D2 family (D2, D3, and D4). Biochemical characterization of the D1-like receptor subtypes has revealed that compared with the D(1A) receptor, the D(1B)/D5 receptor subtype displays properties that resemble those of adrenergic receptors in which mutagenesis of intracellular regions yields constitutively active phenotypes. In other G- protein-coupled receptor systems, such as the rhodopsin and thyroid- stimulating hormone receptors systems, naturally occurring activating mutations lead to pathophysiological manifestations such as retinitis pigmentosa, night blindness, and hyperthyroidism. It is not known if the constitutive activity of the D(1B)/D5 receptor has physiological significance, but the high agonist-independent activity, as well as the increased affinity of this receptor subtype for DA, suggests that this receptor might respond to the endogenous neurotransmitter with intrinsic properties different than those of the related D(1A), receptor.
Tiberi, M; Caron, MG; Carlsson, A
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