Signal transduction through Na+, K+-ATPase impairment involves high affinity neurotensin receptor

VÁZQUEZ C., PEREYRA ALFONSO S., ARMANINO MV., PEÑA C., RODRÍGUEZ DE LORES ARNAIZ G.

Buenos Aires , Argentina

Congreso; XXXIX Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2007

  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.