The role of the GABAB receptor and calcium channels in a Drosophila model of Parkinson's Disease

Transgenic Drosophila melanogaster carrying the human gene for alpha synuclein is an animal model for the study of Parkinson's Disease. Climbing activity in these flies is reduced as a result of the effect of this protein on the locomotor activity of the transgenic fly. l-DOPA and gamma amino butyric acid (GABA) reverse the loss of this activity when placed in the food fed to these flies. While muscimol, a GABAA receptor agonist has no effect in this system, baclofen and the allosteric agonists CG 7930 and GS 39783 which affect the GABAB receptor reverse this activity. This latter effect is eliminated when these compounds are fed in conjunction with the GABAB receptor antagonist 2-hydroxysaclofen. In addition, fendiline which is a Ca++ receptor blocker also reverses the loss of climbing ability. Because there is a calcium channel close to the GABAB receptor on the cell surface, these data are indicative of a relationship between the roles of the GABAB receptor, the calcium channel and the effect of alpha-synuclein on the motor activity of the transgenic fly.

► Human alpha-synuclein reduces the climbing ability in transgenic Drosophila.
► l-DOPA and GABA reverse this effect.
► Agonists of the GABAB receptor also reverse the effect.
► A GABAB receptor antagonist blocks the effect of the agonists.
► The calcium channel blocker fendiline also restores activity.