Acute modulation of somatostatin receptor function by melatonin in the rat frontoparietal cortex.
Since melatonin (N-acetyl-5-methoxytryptamine) decreases locomotor activity and rearing and increases grooming behavior in a similar manner as somatostatin (SRIF), we examined if melatonin could induce these changes through somatostatinergic neurotransmission in the rat frontoparietal cortex. Male Wistar rats (200-250 g) received a single injection of melatonin (25 microg/kg per day) subcutaneously (s.c.) and were sacrificed 5 hr later. Melatonin treatment increased the number of 125I-Tyr11-SRIF receptors in frontoparietal cortical membranes without any changes in the dissociation constant (Kd). The capacity of SRIF to inhibit basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity was increased in melatonin-treated rats as compared to the control animals. Melatonin administration also induced a lower AC activity, both under basal conditions and after stimulation of the enzyme via stimulatory guanine nucleotide-binding proteins (Gs), or directly with FK. Functional inhibitory guanine nucleotide-binding protein (Gi) activity was increased in frontoparietal cortical membranes from melatonin-treated rats when compared to controls. Western blot analyzes showed that melatonin administration did not alter the amount of the Gialpha1, or Gialpha3 subunits, but reduced Gialpha2 levels in frontoparietal cortical membranes. No significant changes in SRIF-like immunoreactivity content and SRIF mRNA levels were detected in this brain area after melatonin treatment. Administration of the melatonin receptor antagonist luzindole (10 mg/kg, s.c.) 30 min before melatonin injection did not change the melatonin-induced effects on the SRIF receptor effector system. In conclusion, the present results show that acute melatonin administration increases the activity of the SRIF receptor effector system and decreases Gialpha2 levels in the rat frontoparietal cortex. In addition, the coupling of Gs to AC is disturbed by melatonin.
Izquierdo-Claros
R M
RM
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Madrid, Spain.
Boyano-Adánez
M C
MC
Torrecillas
G
G
Rodríguez-Puyol
M
M
Arilla-Ferreiro
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D010296:Parietal Lobe / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000187:drug effects* / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; D008550:Melatonin