Effects of single and continuous administration of amyloid beta-peptide (25-35) on adenylyl cyclase activity and the somatostatinergic system in the rat frontal and parietal cortex.
It is unknown whether the amyloid beta-peptide (Abeta), a principal component found in extracellular neuritic plaques in the brain of patients with Alzheimer's disease (AD), is capable of altering adenylyl cyclase (AC) activity and the somatostatin (SRIF) receptor-effector system in the cerebral cortex of the patients. Therefore, the objective of this study was to investigate the effect of the beta fragment, beta (25-35), on AC activity and the somatostatinergic system in the rat frontoparietal cortex. A single dose of beta (25-35) (10microg) injected intracerebroventricularly significantly decreased the density of SRIF receptors (27.4%) and increased their affinity (32.2%) in the frontoparietal cortex. The inhibitory effect of SRIF on basal and forskolin (FK)-stimulated AC activity was significantly lower in the beta (25-35)-treated rats when compared with controls. beta (25-35) did not modify Gialpha1, Gialpha2 nor Gialpha3 levels in membranes from the frontoparietal cortex. Continuous infusion of the peptide induced a decrease in the SRIF receptor density in this brain area to a similar extent as that observed 14 days after the single administration of the peptide. Likewise, this treatment decreased the SRIF receptor density in the frontal cortex (15.3%) and parietal cortex (27.2%). This effect was accompanied by a decrease in the SRIF-mediated inhibition of FK-stimulated AC activity (from 41.6% to 25.6%) in the frontal cortex as well by a decrease in basal AC activity (from 36.9% to 31.6%) and FK-stimulated AC activity (from 35.6% to 27.1%) in the parietal cortex. Continuous infusion of Abeta (25-35) had no effect on Gialpha1, Gialpha2 or Gialpha3 levels in membranes from frontal and parietal cortex. However, this treatment caused a decrease in SRIF-like immunoreactivity content in the parietal (38.9%) and frontal (20.4%) cortex. These results suggest that Abeta might be involved in the alterations of somatostatinergic system reported in AD.
Hervás-Aguilar
A
A
Grupo de Neurobioquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Ctra. Madrid-Barcelona km 33,6, Universidad de Alcalá, E-28871, Alcalá de Henares, Madrid, Spain.
Puebla-Jiménez
L
L
Burgos-Ramos
E
E
Aguado-Llera
D
D
Arilla-Ferreiro
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D005576:Colforsin / Q000494:pharmacology; D003720:Densitometry; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008566:Membranes / Q000378:metabolism; D010296:Parietal Lobe / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism / Q000502:physiology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D017481:Receptors, Somatostatin; C074636:amyloid beta-protein (25-35); D005576:Colforsin; D013004:Somatostatin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases