Glial cells express multiple ATP binding cassette proteins which are involved in ATP release

Rat brain astrocyte and microglia cultures express different members of ATP-binding-cassette (ABC) proteins. RT-PCR analysis showed that astrocytes are equipped with P-glycoprotein (mdrla, mdrlb), multidrug resistance-associated-protein (mrpl, mrp4, mrp5) and cystic fibrosis transmembrane conductance regulator (CFTR). No transcripts for mrp5 and CFTR were detected in microglia. The ABC protein functional activities are shown by the following results: (i) cyclosporin A (50 muM), verapamil (50 muM), probenecid (1 mM) or sulfinpyrazone (2 mM) enhanced [H-3]vincristine accumulation; (ii) cyclosporin A or verapamil but not probenecid or sulfinpyrazone enhanced [H-3]digoxin accumulation; (iii) glibenclamide (100 muM) inhibited Cl-36 efflux from astrocytes. ATP release from glial cells was inhibited by the pretreatment with ABC protein inhibitors indicating that ABC proteins are involved in nucleotide efflux from glial cells which represent the main source of cerebral extracellular purines.