Table 1.
Regulation of DARPP-32 phosphorylation in vitro by 5-HT receptor agonists and antagonists
| Thr34 | Thr75 | Ser137 | |
|---|---|---|---|
| Control | 100 (17.0) | 100 (5.0) | 100 (3.9) |
| Serotonin | 342 (26.7)** | 76 (7.5)** | 141 (6.0)** |
| 5-HT receptor agonists | |||
| PPB (5HT4 agonist) | 218 (36.1)* | 79 (8.8)* | 107 (2.0) |
| EMDT (5HT6 agonist) | 301 (39.5)** | 76 (7.6)** | 103 (5.5) |
| PPB + EMDT | 397 (41.0)** | 70 (3.8)** | 105 (7.9) |
| DOI (5HT2 agonist) | 144 (10.7) | 105 (4.5) | 158 (8.3)** |
| Anpirtoline (5HT1B agonist) | 86 (3.7)* | 102 (22.2) | 93 (10.0) |
| SR 57227 (5HT3 agonist) | 78 (3.5)* | 88 (6.8) | 105 (9.6) |
| 5-HT receptor antagonists | |||
| SDZ 205,557 (5HT4 antagonist) | 94 (16.7) | 103 (17.5) | 102 (8.8) |
| SDZ + serotonin | 257 (34.4)**† | 95 (11.5)† | 129 (5.0)* |
| Ro 04-6790 (5HT6 antagonist) | 90 (8.7) | 101 (12.5) | 105 (7.3) |
| Ro + serotonin | 225 (28.5)*† | 96 (8.4)† | 131 (7.2)* |
| Ro + SDZ | 84 (6.5) | 110 (11.5) | 107 (6.2) |
| SDZ + Ro + serotonin | 198 (44.5)*‡ | 98 (6.1)‡ | 134 (18.1)* |
| Ketanserin (5HT2 antagonist) | 94 (2.9) | 105 (8.9) | 97 (4.8) |
| Ketanserin + serotonin | 322 (28.4)** | 78 (12.1)* | 101 (9.1)† |
| Clozapine (5HT2/6 antagonist) | 124 (19.8) | 101 (13.4) | 105 (5.5) |
| Clozapine + serotonin | 156 (15.4)*‡ | 98 (5.2)‡ | 110 (4.9)† |
Effects of serotonin (100 μM), PPB (100 μM), a 5-HT4 receptor agonist, EMDT (100 μM), a 5-HT6 receptor agonist, DOI (100 μM), a 5-HT2 receptor agonist, anpirtoline, (100 μM), a 5-HT1B receptor agonist, and SR 57227 (100 μM), a 5-HT3 receptor agonist, on Thr34, Thr75, and Ser137. In antagonist experiments, ketanserin (10 μM), a 5-HT2 receptor antagonist, SDZ 205,557 (10 μM), a 5-HT4 receptor antagonist, Ro 04-6790 (10 μM), a 5-HT6 receptor antagonist, or clozapine (10 μM), a multireceptor antagonist with high affinity for 5-HT2 and 5-HT6 receptors, was applied to striatal slices 10 min before serotonin (100 μM). Data represent means (± SEM) (n = 12–30).
, P < 0.05;
, P < 0.01;
, P < 0.001 compared with control;
, P < 0.05;
, P < 0.01 compared with serotonin alone; one-way ANOVA followed by Dunnett's test.