Opiate Receptor Agonists Regulate Phosphorylation of Synapsin I in Cocultures of Rat Spinal Cord and Dorsal Root Ganglion

κ opiate receptor agonists applied to cocultures of spinal cord and dorsal root ganglion neurons have been previously shown to inhibit voltage-dependent Ca2+influx and adenylate cyclase activity. Here we describe the effect of κ opiate receptor agonists on phosphorylation of synapsin I, a synaptic-vesicle-associated protein whose phosphorylation was shown to be regulated by cAMP and Ca2+concentrations. Depolarization of spinal cord-dorsal root ganglion cocultured cells (by high K+or veratridine) and the addition of forskolin (which activates adenylate cyclase) led to increased phosphorylation of synapsin I. Addition of κ opiate agonists attenuated both the depolarization- and the forskolin-induced phosphorylation of synapsin I. This attenuation was blocked by the opiate antagonist naloxone. μ and δ opiate receptor agonists had much weaker effects on the depolarization-induced phosphorylation of synapsin I. Similarly, κ opiate agonists decreased (by 40-60%) the high-K+- or veratridine-induced phosphorylation of synapsin I in spinal cord synaptosomes. These results show that opiate ligands modulate synapsin I phosphorylation. Moreover, the data could explain the reduction in synaptic efficacy observed after opiate treatment.