Acute effects of D1- and D2-receptor agonist and antagonist drugs on somatostatin binding, inhibition of adenylyl cyclase activity and accumulation of inositol 1,4,5-trisphosphate in the rat striatum.
A recent study carried out by our group demonstrated that exogenous dopamine increases the somatostatin (SS) receptor-effector system in the rat striatum. The present study examined the participation of the D1- and D2-dopaminergic systems in the modulation of the rat striatal SS receptor-effector system by use of the D1-receptor agonist and antagonist SKF 38393 and SCH 23390, respectively, and the D2-receptor agonist and antagonist bromocriptine and raclopride, respectively. In view of the rapid onset of dopamine action, the effect of dopaminergic agents on the SS mechanism of action were studied 3 h after their administration. SKF 38393 (4 mg/kg i.p.) or bromocriptine (2 mg/kg i.p.) administered to male Wistar rats increased the number of 125I-Tyr3-SMS receptors in the striatum (52 and 30%, respectively) without changing the affinity constant. The effect of SKF 38393 on 125I-Tyr3-SMS binding was antagonized by the D1-specific antagonist SCH 23390 (0.25 mg/kg i.p.) whereas the effect of bromocriptine was abolished by the D2-specific antagonist raclopride (5 mg/kg i.p.). No change in binding was produced when SKF 38393 or bromocriptine were added directly to the incubation medium. The acute systemic administration of SCH 23390 or raclopride alone had no effect on the binding of 125I-Tyr3-SMS to its receptors. The increase of the number of 125I-Tyr3-SMS receptor induced by SKF 38393 or bromocriptine was accompanied by an increase in the capacity of SMS 201-995 to inhibit basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity when compared to the control groups. In addition, the effect of SMS 201-995 on the mass accumulation of inositol 1,4,5-trisphosphate (IP3) was investigated. SKF 38393 as well as bromocriptine increased the capacity of SMS 201-995 to accumulate IP3 in the rat striatum although this effect was only statistically significant in the case of SKF 38393. These results suggest that the activation of D1 and D2 receptors increases the activity of the SS receptor-effector system, the effect being greater in the case of D1 receptors. These findings are consistent with a functional interaction between dopamine and SS in the rat striatum.
Izquierdo-Claros
R M
RM
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
Boyano-Adánez
M C
MC
Larsson
C
C
Gustavsson
L
L
Arilla
E
E
D000262:Adenylyl Cyclases / Q000187:drug effects*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D017481:Receptors, Somatostatin / Q000187:drug effects*; D013997:Time Factors
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin; D015544:Inositol 1,4,5-Trisphosphate; D000262:Adenylyl Cyclases