Modulation of somatostatin receptors, somatostatin content and Gi proteins by substance P in the rat frontoparietal cortex and hippocampus

Abstract

Substance P (SP) and somatostatin (SRIF) are widely spread throughout the CNS where they play a role as neurotransmitters and/or neuromodulators. A colocalization of both neuropeptides has been demonstrated in several rat brain areas and SP receptors have been detected in rat cortical and hippocampal somatostatinergic cells. The present study was thus undertaken to determine whether SP could modulate SRIF signaling pathways in the rat frontoparietal cortex and hippocampus. A single intraperitoneal injection of SP (50, 250 or 500 lg/kg) induced an increase in the density of SRIF receptors in membranes from the rat frontoparietal cortex at 24 h of its administration, with no change in the hippocampus. The functionality of the SRIF receptors was next investigated. Western blot analysis of Gi proteins demonstrated a significant decrease in Gia 1 levels in frontoparietal cortical membranes from rats treated acutely (24 h) with 250 lg/kg of SP, which correlated with a decrease in functional Gi activity, as assessed by use of the non-hydrolyzable GTP analog 5¢-guanylylimidodiphosphate. SRIF-mediated inhibition of basal or forskolin-stimulated adenylyl cyclase activity was also significantly lower in the frontoparietal cortex of the SP-treated group, with no alterations in the catalytic subunit of the enzyme. SRIF-like immunoreactivity content was increased in the frontoparietal cortex after acute (24 h) SP administration (250 or 500 lg/kg) as well as in the hippocampus in response to 7 days of SP (250 lg/kg) administration. All these SP-mediated effects were prevented by pretreatment with the NK 1 receptor antagonist RP-67580. Although the physiologic significance of these results are unknown, the increase in SRIF receptor density together with the desensitization of the SRIF inhibitory signaling pathway might be a mechanism to potentiate the stimulatory pathway of SRIF, inducing a preferential coupling of the receptors to PLC.

Minocycline prevents Aβ(25–35)-induced reduction of somatostatin and neprilysin content in rat temporal cortex

“…In the current study, the SRIF-LI levels in the control animals, as determined by radioimmunoassay, were similar to those previously reported by our group and other authors (Patel and Reichlin, 1978;Puebla and Arilla-Ferreiro, 2003;Hervás-Aguilar et al, 2005;BurgosRamos et al, 2007). Continuous i.c.v.…”

Chronic but not acute intracerebroventricular administration of amyloid β‐peptide(25–35) decreases somatostatin content, adenylate cyclase activity, somatostatin‐induced inhibition of adenylate cyclase activity, and adenylate cyclase I levels in the rat hippocampus

“…The SRIF‐LI content in the hippocampus of control rats was similar to that previously reported by our group (Puebla and Arrila‐Ferreiro,2003) and by others (Srikant and Patel,1981). The present study demonstrates that chronic i.c.v.…”

Effects of single and continuous administration of amyloid β-peptide (25–35) on adenylyl cyclase activity and the somatostatinergic system in the rat frontal and parietal cortex

“…The SRIF-LI levels in the control animals, as determined by radioimmunoassay, were similar to those previously reported by our group and other authors (Patel and Reichlin, 1978;Puebla and Arilla, 2003). Continuous infusion of A␤ (25-35) led to a reduction in the SRIF-LI content in the frontoparietal cortex as well as in the frontal and parietal cortex when studied separately.…”