Distribution of neurotensin-like immunoreactivity (NTLI) and neurotensin receptor in the rat brain and effects of various drugs on NTLI concentration and NT receptor in the rat cerebral cortex

Abstract

A radioimmunoassay for neurotensin(NT) and binding assay for NT receptor have been developed to determine neurotensin-like immunoreactivity (NTLI) concentration and to characterize NT receptor in the rat brain. The effect of various drugs affecting the dopaminergic system in the brain were also investigated to clarify the relationship between NT and dopamine. NTLI was widely distributed in various regions of the rat brain: the highest level was 53.1 +/- 14.1 ng/g wet wt in the hypothalamus, 11.9 +/- 6.0 ng/g wet wt in the thalamus, 6.9 +/- 0.7 ng/g wet wt in the cerebral cortex and 0.7 +/- 0.2 ng/g wet wt in the cerebellar cortex. The Bmax of NT receptor was 20.2 +/- 4.6 fmol/mg protein in the cerebral cortex, 16.0 +/- 4.9 fmol/mg protein in the hypothalamus, 13.3 +/- 3.7 fmol/mg protein in the thalamus and no detectable level in the cerebellar cortex. The Kd of NT receptor was 2.7 +/- 0.7 nM in the cerebral cortex, 1.9 +/- 0.8 nM in the hypothalamus, 1.1 +/- 0.2 nM in the thalamus. Intraperitoneal(ip) bolus administration of L-DOPA caused the reduction in NTLI concentration from 9.2 +/- 1.0 ng/g wet wt to 5.3 +/- 2.1 ng/g wet wt and Bmax of NT receptor from 19.7 +/- 3.1 fmol/mg protein to 13.9 +/- 2.6 fmol/mg protein with no change in Kd. Intracerebroventricular administration of dopamine also induced a significant reduction of NTLI concentration and Bmax of NT receptor with no change in Kd. Inversely, ip bolus administration of alpha-methyldopa evoked an increase in NTLI concentration from 6.9 +/- 0.9 ng/g wet wt to 12.0 +/- 3.0 ng/g wet wt and that in Bmax of NT receptor from 15.9 +/- 2.9 fmol/mg protein to 24.2 +/- 4.6 fmol/mg protein. Serial administration of haloperidol evoked an increase in Bmax of NT receptor from 16.9 +/- 1.5 fmol/mg protein to 20.5 +/- 1.9 fmol/mg protein with no changes in Kd and NTLI concentration. These results suggest that dopamine may modulate the action of NT in the rat cerebral cortex.