The present study describes the characterization of the binding properties and autoradiographic distribution of a new nonpeptide antagonist of neurotensin receptors, [3H]SR 142948A (2-[[5-(2,6-dimethoxyphenyl)-1-(4-(N-(3-dimethylaminopropyl)-N-methyl carbamoyl)-2-isopropylphenyl)-1H-pyrazole-3-carbonyl]-amino]-ad amantane-2-carboxylic acid, hydrochloride), in the rat brain. The binding of [3H]S...

In female mammals, increased ovarian estradiol (E(2)) secretion triggers GnRH release from neurons in the basal forebrain, which drives LH secretion from the pituitary and subsequently induces ovulation. However, the neural circuits that activate this preovulatory GnRH/LH surge remain unidentified. Neurotensin is expressed in neurons of the anteroventral periventricular nucleus (AVPV), a region...

BACKGROUND Purification of recombinant membrane receptors is commonly achieved by use of an affinity tag followed by an additional chromatography step if required. This second step may exploit specific receptor properties such as ligand binding. However, the effects of multiple purification steps on protein yield and integrity are often poorly documented. We have previously reported a robust tw...

We investigated whether chronic subcutaneous infusion of neurotensin during 14 days would affect pancreatic and gastric growth of rats. In another experiment, neurotensin (836 pmol/kg) was injected intraperitoneally three times a day for three days in 12 rats. Thereafter, pancreatic DNA and in vitro incorporation of 3H-thymidine into pancreatic DNA was determined. Long term infusion of 282 pmol...

In order to determine whether glutamate is enriched in neurotensin-containing axons in the superficial dorsal horn of the rat spinal cord, we have carried out preembedding immunocytochemistry with an antiserum to neurotensin and then used a postembedding immunogold method with antiserum to glutamate. The immunogold label (corresponding to glutamate-like immunoreactivity) over 40 neurotensin-imm...

The effects of neurotensin upon blood pressure in conscious rats were examined after intracerebroventricular (i.v.t.) or intravenous (i.v.) administration of this peptide. Whereas i.v. injected neurotensin (0.1-2.0 microgram/kg) was depressor, i.v.t. injected neurotensin (1 microgram and above) was pressor. Peripheral depressor responses could not be repeated in the same animal due to tachyphyl...

Neurotensin has been shown to inhibit gastric acid secretion when administered in pharmacological doses, but no information has been available concerning its possible dose-related effect during intravenous infusion. In this study, a dose-related and reversible inhibitory effect of neurotensin was demonstrated in pentobarbital-anesthetized female Sprague-Dawley rats. The rats underwent continuou...

1. Neurotensin was infused intravenously, in the presence or absence of intravenous atropine or intraarterial tetrodotoxin, into dogs anaesthetized with sodium pentobarbitone. Net and unidirectional fluxes of sodium and blood flows in the ileum were measured. Arterial and mesenteric venous blood pressures, haematocrits and plasma total solids were also determined. 2. Neurotensin caused a transi...

The role of intracellular cAMP and protein kinase A in dopamine-induced inhibition of dopamine neurons and the attenuation of this inhibition by neurotensin were studied in rat midbrain slices. Spontaneous activity of dopamine cells was recorded extracellularly from both the ventral tegmental area and the substantia nigra. Perfusion of the slices with 8-bromo-cAMP and forskolin significantly at...

Emerging evidence supports neurotensin as a trophic and antiapoptotic factor, mediating its control via the high-affinity neurotensin receptor (NT1 receptor) in several human solid tumors. In a series of 51 patients with invasive ductal breast cancers, 34% of all tumors were positive for neurotensin and 91% positive for NT1 receptor. We found a coexpression of neurotensin and NT1 receptor in a ...