Influence of fluoxetine and p-chloroamphetamine on the somatostatin receptor-adenylyl cyclase system in the rat frontoparietal cortex.
There is evidence that suggests a reciprocal functional link between the serotonergic and the somatostatinergic system in the rat frontoparietal cortex. However, to date, the role of endogenous 5-hydroxytryptamine (serotonin) on the regulation of the somatostatin (SS) receptor-adenylyl cyclase (AC) system remains unclear. In the present study, the administration of fluoxetine (10 mg/kg i.p.), a 5-hydroxytryptamine uptake inhibitor in a single dose or administered daily for 14 days increased the number of specific [125I]Tyr11-SS receptors, with no change in the receptor affinity, in rat frontoparietal cortical membranes. However, the capacity of SS to inhibit forskolin (FK)-stimulated AC activity in these membranes was lower than in the control groups. The ability of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp(NH)p) to inhibit FK-stimulated AC activity in frontoparietal cortical membranes was also decreased in rats acutely and chronically treated with fluoxetine. p-Chloroamphetamine (5 mg/kg i.p.), which leads to a lasting reduction of 5-hydroxytryptamine innervation, administered on days 1, 3 and 5 and the rats sacrificed 1 or 3 weeks after the first injection, decreased the number of SS receptors without changing the receptor affinity. In this experimental group, SS also caused a significantly lower inhibition of FK-stimulated AC activity. p-Chloroamphetamine had no effect on the ability of Gpp(NH)p to inhibit FK-stimulated AC activity in frontoparietal cortical membranes at all the time periods studied. The present results suggest that under normal circumstances some SS receptors are under a tonic stimulatory control through the serotonergic system.
Muñoz-Acedo
G
G
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
Izquierdo-Claros
R M
RM
Puebla
L
L
Rodríguez-Martín
E
E
Arilla
E
E
D000262:Adenylyl Cyclases / Q000187:drug effects*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects*; D010296:Parietal Lobe / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D018687:Antidepressive Agents, Second-Generation; D017481:Receptors, Somatostatin; D005473:Fluoxetine; D013004:Somatostatin; D010133:p-Chloroamphetamine; D000262:Adenylyl Cyclases