Focusing on the dopaminergic system is of use for several clinical conditions, including psychiatric disorders as psychoses, and neurological disorders, as Parkinson-related diseases. The dopaminergic receptors are G-protein coupled receptors (GPCR), where the first step following receptor activation is an exchange of GDP for GTP at the a-subunit of the G-protein. To assess the functionality of these systems, approaches for the study of GPCR have been developed, as the agonist-induced GTPase activities, and the agonist-induced [³⁵S]GTPgS binding. They focus on the first step of the signal transduction cascade. We are focusing on the [³⁵S]GTPgS binding, induced by dopaminergic agonists and partial agonists, on naïve rodent striatal homogenates, in order to compare and understand the functional characteristics of these compounds.

In this case, we mentioned that determining the optimal conditions to observe an agonist or partial agonist-induced [³⁵S]GTPgS binding, depends on different parameters, considering the type of molecule used: incubation time, GDP concentration, ions in the buffers. Each of this parameter influences the agonist-induced nucleotide binding.

Herein, we would like to provide our data concerning the optimization of the dopaminergic partial agonists and agonists-induced [³⁵S]GTPgS binding, focusing especially on the role of GDP. The optimization of GDP concentrations required to obtain the most efficacious dopaminergic-induced [³⁵S]GTPgS binding could be of relevance to hypothesize that agonists acting on the same receptors could recruit different G-protein, emphasizing then the concept of functional selectivity. It could then be suggested that different compounds having the same properties for a receptor, could induce different second messenger pathways, explaining then the variations in their efficacy and in their secondary effects.