Specific heterotrimeric G-protein type regulation is tissue-dependent for VMAT2; it is not known whether this is the case for VMAT1. Heterotrimeric G-protein Gαo2 decreases VMAT1 activity in pancreatic and adrenal medulla cells, and activates heterotrimeric G-proteins inhibit VMAT2 activity in the brain, regardless of whether localised on small clear-core or large-dense-core vesicles. Activated heterotrimeric G-protein Gαq downregulates VMAT2 mediated serotonin transport in blood platelets, but this is not the case in the brain where Gαq inhibits VMAT2 activity completely. Although the exact signalling pathway for G-protein mediated regulation of VMATs is not known, it has recently been described that implicated G-proteins act directly on the VMATs themselves.