SIGNAL TRANSDUCTION THROUGH Na+, K+-ATPase IMPAIREMENT INVOLVES HIGH AFFINITY NEUROTENSIN RECEPTOR

C. VÁZQUEZ; S. PEREYRA-ALFONSO; M. V. ARMANINO; C. PEÑA; G. RODRÍGUEZ DE LORES ARNAIZ

Buenos Aires

Congreso; XXXIX Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); 2007

Asociación Argentina de Farmacología Experimental (SAFE)

Phosphoinositide (PI) metabolism is enhanced in neonatal brain by activation of neurotransmitter receptors and by inhibition of the sodium pump with ouabain (Oua) or endogenous inhibitor, endobain E (End E). Neurotensin inhibits synaptosomal membrane Na+, K+-ATPase activity, an effect blocked by SR 48692 (SR), a selective antagonist for high-affinity neurotensin receptor (NTS1). To evaluate potential participation of NTS1 on PI hydrolysis enhancement by sodium pump inhibition, cerebral cortex miniprisms from neonatal Wistar rats were preincubated for 0 or 30 min in the absence or presence of SR; then, Oua or End E were added and incubation proceeded for 20 or 60 min. After 60-min incubation with Oua, IPs accumulation vs basal was 500% or 860% if preincubation was omitted or lasted 30 min, respectively; values were reduced 50% in the presence of SR. With 20 min incubation, IPs accumulation by Oua vs basal was 300% or 410% if preincubation was 0 or 30 min, respectively, an effect blocked 23% or 32% with SR. PI hydrolysis enhancement by End E was similarly blocked by SR, being higher when incubation with End E lasted 60 vs 20 min. PI turnover increase by sodium pump inhibition with Oua or End E is diminished by SR suggesting that, at least partially, NTS1 is involved in this signaling system.