Altered ligand binding of D1 and D2 dopamine receptors in response to hypoxia and posthypoxic reoxygenation.

Abstract

The physiological effects of dopamine, a major striatal neurotransmitter, are mediated by several distinct receptor subtypes. On the basis of structural, pharmacological, functional, and distributional similarities, these subtypes fall into one of two groups, the D1-like receptor family and the D2-like receptor family. The D1-like receptors are linked to stimulation of adenylate cyclase via Gs proteins whereas the D2-like receptors inhibit adenylate cyclase through a Gi/o protein.1 The D1-like receptors are also associated with inositol phosphate production and calcium mobilization while the D2-like receptors stimulate potassium efflux and indirectly inhibit inositol phosphate production. Thus, changes in the properties of these dopaminergic receptors could have a major impact on cellular metabolism. Several studies have examined the effect of ischemia-hypoxia on ligand binding properties of the striatal dopaminergic receptors, particularly on adult animals, and the authors suggested that the changes in the D1 and/or D2 receptors play a key role in the pathogenesis of damage to the striatum induced by ischemia. For example, Bonfenati et al.4 proposed that reduction in the number of D1 receptors plays a key role in the pathogenesis of ischemic striatal damage. The purpose of the present study was to determine whether arterial hypoxia is associated with alterations in the affinities (Kd) and numbers (Bmax) of the dopaminergic receptor subtypes, D1 and D2, in the striatum of newborn piglets.KeywordsDopamine ReceptorDopaminergic ReceptorNewborn PigletInositol Phosphate ProductionReoxygenation PeriodThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.