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. 2013 Jan;344(1):253–263. doi: 10.1124/jpet.112.199844

Fig. 3.

Fig. 3.

Effect of inhibitors of G protein-coupled receptor kinase-2 (GRK2), conventional protein kinase C (cPKC), and dynamin on long-duration application of neurotensin and quinpirole. Relative change in the firing rate (mean ± S.E.M.) is plotted as a function of time. (A) effect of β-ARK1 inhibitor on long-duration application of quinpirole and neurotensin (10 nM). Quinpirole (54 ± 8.5 nM) alone produced a sustained, statistically significant inhibition in the firing rate over the duration of quinpirole application (□, n = 10) (one-way repeated measures ANOVA, F(7,63) = 11.2, P < 0.05). With 10 nM neurotensin in the superfusate (○, n = 9), there was a statistically significant difference in the magnitude of quinpirole inhibition at the 25- and 40-minute time points compared with the 10-minute time point, indicating reversal of inhibition (one-way repeated measures ANOVA, F(7,35) = 4.0, P < 0.05). In the presence of 10 nM neurotensin in the superfusate and 300 μM β-ARK1 inhibitor in the recording pipette (●, n = 6), no reversal and no significant increase in inhibition in the firing rate produced by quinpirole were observed ([quinpirole] = 125 ± 8.26 nM) (one-way repeated measures ANOVA, F(7,35)= 3.33, P > 0.05). (B) effect of β-ARK1 inhibitor on long-duration application of quinpirole and neurotensin (5 nM). The effect of quinpirole alone (□ and dashed line) from A is shown for comparison. With 5 nM neurotensin in the superfusate (∇, n = 7), no significant inhibition produced by quinpirole (60.7 ± 9.2 nM) was observed (one-way repeated measures ANOVA, F(7,42) = 1.25, P > 0.05); there was a partial reversal in the magnitude of quinpirole inhibition over time. In the presence of 5 nM neurotensin in the superfusate and 300 μM β-ARK1 inhibitor in the recording pipette (▾, n = 8), quinpirole (45.83 ± 3.71 nM) produced a statistically significant inhibition in the firing rate over the time course (one-way repeated measures ANOVA, F(7,49)= 4.16, P < 0.05). (C) effect of Gö6976 on long-duration application of quinpirole and neurotensin (10 nM). The effect of quinpirole alone (□ and dashed line) and quinpirole in the presence of 10 nM neurotensin (▪ and dashed line) from A are shown for comparison. In the presence of 10 μM Gö6976 in the recording pipette and neurotensin in the superfusate (●, n = 5), no significant quinpirole inhibition reversal was observed ([quinpirole] = 64 ± 34.1 nM) (one-way repeated measures ANOVA, F(7,28)= 87.9, P < 0.05). (D) effect of dynasore on long-duration application of quinpirole and neurotensin. The effect of quinpirole alone (□ and dashed line) and quinpirole in the presence of 10 nM neurotensin (▪ and dashed line) from A are shown for comparison. In the presence of 10 nM neurotensin in the superfusate and 800 µM dynasore in the recording electrode (▾, n = 7), no reversal of quinpirole-induced inhibition was observed; quinpirole (75 ± 12.2 nM) produced a statistically significant inhibition in the firing rate over time (one-way repeated measures ANOVA, F(7,42) = 6.91, P < 0.05).