The toxic effects of manganese on dopamine D2 receptor activation is not due to inactivation of the phospholipase C receptor signal transduction component (1143.7)

Manganese (Mn), a neurotoxin causing Manganism a Parkinsons‐like disease, disrupts dopamine (DA) neurons, but the neurotoxic mechanism is not fully resolved. Reports postulate it more related to DA neuron dysfunction than degeneration. Lateral gill cilia of Crassostrea virginica are controlled by serotonergic‐dopaminergic innervations from their ganglia. DA causes cilio‐inhibition, serotonin (HT) cilio‐excitation. We showed post‐synaptic DA receptors in gill lateral cells are D2 type and Mn blocks effects of DA by blocking DA post‐synaptic receptors. The adenylyl cyclase component of the D2 signal transduction pathway was not effected by Mn. Phospholipase C (PLC), another component of the D2 signal transduction pathway, is inactivated by DA. We hypothesized PLC is not effected by Mn. We measured cilia beating using stroboscopic microscopy. Adding HT (10‐6 ‐ 10‐3M) to gill increased beating to 25 beats/min. Adding DA (10‐6 ‐ 10‐3M) decreased rates to 0. Mn (100 µM) prevented the cilio‐inhibitory response. m3M3FBS (10‐6 ‐ 10‐3M), a PLC activator, increased beating. U73122 (10‐6 ‐ 10‐4M), a PLC inhibitor, decreased beating. Mn (100 µM) had no effect on the actions of either drug. The study helps elucidate the neurotoxic mechanism of action of Mn by showing Mn disrupts dopamine’s actions at D2 post‐synaptic receptors, but not at the level of adenylyl cyclase or PLC in the signal transduction pathway.