RT info:eu-repo/semantics/article
T1 Hippocampal somatostatin receptors and modulation of adenylyl cyclase activity in histamine-treated rats
A1 Puebla Jiménez, Lilian
A1 Rodríguez Martín, Eulalia
A1 Arilla Ferreiro, Eduardo
K1 Histamine
K1 Somatostatin receptor
K1 Adenylyl cyclase
K1 G-protein
K1 Hippocampus
K1 Bioquímica
K1 Biochemistry
K1 Science
K1 Ciencia
AB In the present study, the effects of an intracerebroventricular (i.c.v.) dose of histamine (0.1, 1.0 or 10.0 ¿g) on the hippocampal somatostatin (SS) receptor/effector system in Wistar rats were investigated. In view of the rapid onset of histamine action, the effects of histamine on the somatostatinergic system were studied 2 h after its administration. Hippocampal SS-like immunoreactivity (SSLI) levels were not modified by any of the histamine doses studied. SS-mediated inhibition of basal and forskolin (FK)-stimulated adenylyl cyclase (AC) activity was markedly increased in hippocampal membranes from rats treated with 10 ¿g of histamine (23% ± 1% vs. 17% ± 1% and 37% ± 2% vs. 23% ± 1%, respectively). In contrast, neither the basal nor the FK-stimulated enzyme activities were affected by histamine administration. The functional activity of the hippocampal guanine-nucleotide binding inhibitory protein (G(i) protein), as assessed by the capacity of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp[NH]p) to inhibit FK-stimulated AC activity, was not modified by histamine administration. These data suggest that the increased response of the enzyme to SS was not related to an increased functional activity of G(i) proteins. In fact, the increased AC response to SS in hippocampal membranes from histamine (10 ¿g)-treated rats was associated with quantitative changes in the SS receptors. Equilibrium binding data obtained with [125I]Tyr11-SS indicate an increase in the number of specific SS receptors (541 ± 24 vs. 365 ± 16 fmol/mg protein, P < 0.001) together with a decrease in their apparent affinity (0.57 ± 0.04 vs. 0.41 ± 0.03 nM, P < 0.05) in rat hippocampal membranes from histamine (10 ¿g)-treated rats as compared to control animals. With the aim of determining if these changes were related to histamine binding to its specific receptor sites, the histaminergic H1 and H2 receptor antagonists mepyramine and cimetidine, respectively, were administered 1 h before histamine injection. The pretreatment with mepyramine or cimetidine induced an increase in the number and affinity constant of the SS receptors whereas the simultaneous pretreatment with both histamine antagonists prevented the histamine-induced changes in SS binding to its receptors. Since the hippocampal SS receptor/effector system is modulated by histamine, it is tempting to speculate that in the hippocampus, SS could be involved as a mediator of the histamine effects on behaviors such as learning and memory.
PB Elsevier
SN 0169-328X
YR 1996
FD 1996
LK http://hdl.handle.net/10017/2273
UL http://hdl.handle.net/10017/2273
LA eng
NO This work was supported by a Grant from the Dirección General de lnvestigación Científicay Técnica of Spain.
DS MINDS@UW
RD 26-abr-2024