A D2 Class Dopamine Receptor Transactivates a Receptor Tyrosine Kinase to Inhibit NMDA Receptor Transmission

Abstract

Receptor tyrosine kinases (RTKs) are membrane spanning proteins with intrinsic kinase activity. Although these receptors are known to be involved in proliferation and differentiation of cells, their roles in regulating central synaptic transmission are largely unknown. In CA1 pyramidal neurons, activation of D2 class dopamine receptors depressed excitatory transmission mediated by the NMDA subtype of glutamate receptor. This depression resulted from the quinpirole-induced release of intracellular Ca 2+ and enhanced Ca 2+-dependent inactivation of NMDA receptors. The dopamine receptor-mediated depression was dependent on the “transactivation” of PDGFRβ. Therefore, RTK transactivation provides a novel mechanism of communication between dopaminergic and glutamatergic systems and might help to explain how reciprocal changes in these systems could be linked to the deficits in cognition, memory, and attention observed in schizophrenia and attention deficit hyperactivity disorder.