Dopamine enhances somatostatin receptor-mediated inhibition of adenylate cyclase in rat striatum and hippocampus.
Although there is evidence that suggests that dopamine (DA) has stimulatory effects on somatostatinergic transmission, it is unknown to date if DA increases the activity of the somatostatin (SS) receptor-effector system in the rat brain. In this study, we evaluated the effects of the administration of DA and the DA D1-like (D1, D5) receptor antagonist SCH 23390 and the D2-like (D2, D3, D4) receptor antagonist spiperone on the SS receptor-adenylate cyclase (AC) system in the Sprague-Dawley rat striatum and hippocampus. An intracerebroventricular injection of DA (0.5 microgram/rat) increased the number of SS receptors and decreased their apparent affinity in the striatum and hippocampus 15 hr after its administration. The simultaneous administration of the DA receptor antagonists SCH 23390 (0.25 mg/kg, ip) and spiperone (0.1 mg/kg, ip) before DA injection partially prevented the DA-induced increase in SS binding. The administration of SCH 23390 plus spiperone alone produced a significant decrease in the number of SS receptors in both brain areas studied at 15 hr after injection, an effect that disappeared at 24 hr. The increased number of SS receptors in the DA-treated rats was associated with an increased capacity of SS to inhibit basal and forskolin (FK)-stimulated (AC) activity in the striatum and hippocampus at 15 hr after injection. This effect had disappeared at 24 hr. By contrast, basal and FK-stimulated enzyme activities were unaltered after DA injection. No significant changes in the levels of the alpha i (alpha i1 + alpha i2) subunits were found in DA-treated rats as compared with control rats. In addition, the immunodetection of the alpha i1 or alpha i2 subunits showed no significant changes in their levels in DA-treated rats when compared with controls. DA injection also induced an increase in SS-like immunoreactive content in the rat striatum but not hippocampus at 15 hr after administration and returned to control values at 24 hr. These results provide direct evidence of a functional linkage between the dopaminergic and somatostatinergic systems at the molecular level.
Rodríguez-Sánchez
M N
MN
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá de Henares, Madrid, Spain.
Puebla
L
L
López-Sañudo
S
S
Rodríguez-Martín
E
E
Martín-Espinosa
A
A
Rodríguez-Pena
M S
MS
Juarranz
M G
MG
Arilla
E
E
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007158:Immunologic Techniques; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D001552:Benzazepines; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D017481:Receptors, Somatostatin; D005576:Colforsin; D013134:Spiperone; D013004:Somatostatin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D004298:Dopamine