alpha-Fluoromethylhistidine influences somatostatin content, binding and inhibition of adenylyl cyclase activity in the rat frontoparietal cortex.
Slow-wave sleep, wakefulness, locomotor activity and learning and memory are regulated in similar ways by somatostatin (SS) and histamine. To clarify the possible role of endogenous histamine on the somatostatinergic system of the rat frontoparietal cortex, we studied the effect of 50 micrograms of alpha-fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, administered intracerebroventricularly (i.c.v.) at 1, 4 and 6 h, on somatostatin-like immunoreactivity (SSLI) content and the SS receptor/effector system. The histamine content in the frontoparietal cortex decreased to about 67, 60 and 72% of control values at 1, 4 and 6 h after alpha-FMH administration, respectively. At 6 h after alpha-FMH injection, there was an increase in SSLI content and a decrease in the number of SS receptors, with no change in the apparent affinity. No significant differences were seen for the basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activities in the frontoparietal cortex of alpha-FMH-treated rats when compared to the control group at all times studied. At 6 h after alpha-FMH administration, however, the capacity of SS to inhibit basal and FK-stimulated AC activity in the frontoparietal cortex was significantly lower than in the control group. The ability of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp(NH)p) to inhibit FK-stimulated AC activity in frontoparietal cortex membranes was the same in the alpha-FMH-treated (6 h) and control animals. Therefore, the decreased SS-mediated inhibition of AC activity observed in the alpha-FMH-treated rats is not due to an alteration at the guanine nucleotide-binding inhibitory protein (Gi) level but rather may be due to the decrease in the number of SS receptors. Taken together, these data suggest that alpha-FMH influences the sensitivity to SS in the rat frontoparietal cortex.
Puebla
L
L
Unidad de Neuroendocrinología Molecular, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
Arilla
E
E
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008762:Methylhistidines / Q000494:pharmacology*; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D008762:Methylhistidines; D013004:Somatostatin; C028309:alpha-fluoromethylhistidine; D000262:Adenylyl Cyclases