NEUROTENSIN RECEPTOR (NTS1) IS INVOLVED IN PHOSPHOINOSITIDE HYDROLYSIS ENHANCEMENT BY Na/K ATPase INHIBITION.

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

Madison, Wisconsin, EE.UU.

Congreso; XXXVI Congreso de la Sociedad Americana de Neuroquímica (ASN), Madison, Wisconsin, EE.UU.; 2005

Sociedad Americana de Neuroquímica (ASN)

Phosphoinositide (PI) metabolism is enhanced in brain by ouabain, a sodium pump inhibitor. Previous results showed that neurotensin inhibits this pump, an effect blocked by SR 48692, a selective antagonist for NTS1. We evaluated potential role of NTS1 receptor on PI hydrolysis enhancement by sodium pump inhibition. Neonatal rat brain prisms were incubated with [3H]myoinositol in buffer during 60 min. Then, incubation continued (20 or 60 min) with 10-4 M SR 48692 and/or 10-4 M ouabain. In other series of experiments, prisms were preincubated 30 min in the presence or absence of SR 48692, when ouabain was added and incubation proceeded for 20 or 60 min. Reaction was stopped with cloroform/methanol and [3H]inositol-phosphates (IPs) accumulation quantified. With respect to basal values (100%) IPs accumulation achieved after 20 and 60 min incubation with ouabain was respectively 299±22.2% and 497±61.7%; in the presence of SR 48692, these values were diminished 25% and 50%. If samples were preincubated for 30 min and later incubated for 20 or 60 min, IPs accumulation by ouabain attained 411±9.6% and 861±67.5%, respectively; these values were diminished 32% and 52% with SR 48692. Similar results were recorded when ouabain was replaced by an endogenous sodium pump inhibitor termed endobain E. Results showed that PI turnover increase by ouabain is diminished by SR 48692 indicating that NTS1 receptor is involved in PI hydrolysis enhancement by pump inhibition.