Intracellular recordings were obtained from supraoptic magnocellular neurosecretory cells (MNCs) in superfused explants of rat hypothalamus. Application of ATP and UTP, but not adenosine, produced TTX-insensitive depolarizations accompanied by increases of input conductance. 2. The P2X agonists alpha,beta-methylene ATP, beta,gamma-methylene ATP and 2-methylthio ATP mimicked the effects of ATP in > 77% of the cells tested. Depolarizing responses to ATP were reversibly inhibited by PPADS (pyridoxal-phosphate-6-azophenyl-2',4'- disulphonic acid; IC50 approximately 0.5 microM), a selective P2X antagonist. 3. The reversal potential of responses to ATP (-37 mV) was not strongly affected by intracellular Cl- injection or by removal of Cl- from the external solution. The reversal potential of responses to the most potent P2X agonist, alpha,beta-methylene ATP, was -29 mV. These values suggest the involvement of non-selective cationic channels, a finding which is consistent with the ionotropic cationic channel structure of cloned P2X purinoceptors. 4. The reversal potential of UTP-mediated responses (-33 mV) was also consistent with the involvement of non-selective cationic channels. Since cloned P2U receptors display homology with G-protein-coupled receptors, cationic channels modulated by UTP are probably different from those mediating P2X responses.
