Figure 9. Effects of MAO_A and COMT inhibition on the radioactive outflow in cultures loaded with [³H]-NA.

A, radioactive outflow in response to 0.5 μM cyanine 863 (application indicated by bar) from control SCG cultures (○) and from matched cultures treated with the MAO_A inhibitor clorgyline (0.5 μM, •) 10 min before and during the collection of fractions. Results are shown as fractional rates (means ± s.e.m., n = 3). B, radioactive outflow in response to 0.3 μM reserpine (application indicated by bar) from control SCG cultures (○) and from matched cultures treated with clorgyline as in A (0.5 μM, •). Results are shown as mean fractional rates (s.e.m. values smaller than the size of symbols, n = 3). C, AUC values of radioactive outflow induced by indicated test substances. OR 486 + Clorgyl: cultures treated for 10 min with 1 μM of the COMT inhibitor OR 486 plus 0.5 μM clorgyline before and during the collection of fractions. Res (without enzyme inhibitors): 0.3 μM reserpine (transiently applied for 8 min as shown in B and in Fig. 7A). Data shown by the open bar are taken from Fig. 7C for a comparison, n = 37. Res (OR 486 + Clorgyl): radioactive outflow induced by 0.3 μM reserpine transiently applied in the presence of enzyme inhibitors (n = 17). Data differ significantly from results of reserpine-induced radioactive outflow without enzyme inhibitors, P < 0.01, Mann-Whitney U test. Des (OR 486 + Clorgyl): radioactive outflow induced by 0.5 μM desipramine in the presence of enzyme inhibitors (n = 26). Res Des (OR 486 + Clorgyl): radioactive outflow induced by 0.3 μM reserpine followed by 0.5 μM desipramine in the presence of enzyme inhibitors (n = 24). Data of combined applications differ significantly from results of release induced by reserpine or desipramine alone, P < 0.01, Mann-Whitney U test. Res Des Cy 2.0 (OR 486 + Clorgyl): radioactive outflow induced by 0.3 μM reserpine, followed by 0.5 μM desipramine plus 2.0 μM cyanine 863 in the presence of enzyme inhibitors (n = 24). D, Cy 0.5 (without enzyme inhibitors): radioactive outflow induced by 0.5 μM cyanine 863 (n = 9). Cy 0.5 (Clorgyl): radioactive outflow in response to 0.5 μM cyanine 863 with MAO_A inhibited (n = 8). Data differ significantly from results of cyanine 863-induced release without the inhibition of MAO_A, P < 0.01, Mann-Whitney U test. Des Cy 2.0 (OR 486 + Clorgyl): release induced by 2.0 μM cyanine 863 with both MAO_A and COMT inhibited, and with 0.5 μM desipramine included in the superfusion buffer 10 min before and during the application of cyanine 863 (n = 9; data points significantly different from zero, P < 0.01, Mann-Whitney U test).