In vivo studies with low doses of levocabastine and diphenhydramine, but not pyrilamine, antagonize neurotensin-mediated antinociception.

The present study describes in vivo experiments in the rat addressing the role of levocabastine, and two other specific histamine H1 antagonists, diphenhydramine and pyrilamine, at neurotensin (NT)-mediated hypothermia and antinociception (hotplate). Levocabastine given i.p.

Pharmacological profile of antidepressants and related compounds at human monoamine transporters.

Using radioligand binding assays, we determined the equilibrium dissociation constants (KD's) for 37 antidepressants, three of their metabolites (desmethylcitalopram, desmethylsertraline, and norfluoxetine), some mood stabilizers, and assorted other compounds (some antiepileptics, Ca2+ channel antagonists, benzodiazepines, psychostimulants, antihistamines, and monoamines) for the human serotonin, norepinephrine, and dopamine transporters. Among the compounds that we tested, mazindol was the most potent at the human norepinephrine and dopamine transporters with KD's of 0.45 +/- 0.

The expression of mRNA for a kappa opioid receptor in the substantia nigra of Parkinson's disease brain.

We molecularly cloned the kappa opioid receptor from a human substantia nigra cDNA library. When expressed in HEK293 cells, the cloned receptor had similar pharmacological characteristics to the rat kappa opioid receptor. Northern blot analysis showed the presence of a single transcript of about 6 kb in size for mRNA prepared from the substantia nigra.

Characterization of the genomic structure, promoter region, and a tetranucleotide repeat polymorphism of the human neurotensin receptor gene.

In the present study, we have cloned the human neurotensin receptor (NTR) gene, determined its structure, demonstrated that its promoter is functional in transfection experiments, and identified the start site of transcription and a tetranucleotide repeat polymorphism that locates at less than 3 kilobase pairs from the gene. The gene contains three introns, all in the coding regions. Several differences in genomic clones and previously characterized cDNA sequences are reconciled.

Proposed ligand binding site of the transmembrane receptor for neurotensin(8-13).

We report here the first proposed ligand binding site of the transmembrane receptor for neurotensin(8-13) in human and rat, the corresponding bound conformation of the peptide ligand, and site-directed mutagenesis studies that support the binding site model. These three-dimensional structures were generated by using a heuristic approach in conjunction with experimental data. The proposed neurotensin(8-13) binding site is primarily composed of eight residues (i.

Chimeric rat/human neurotensin receptors localize a region of the receptor sensitive to binding of a novel, species-specific, picomolar affinity peptide.

Recently, we reported the development of a species-specific neurotensin analog that displays selective binding affinity at the rat and human neurotensin (NT) receptor, L-[3,2'-Nal11]NT(8-13) (where Nal is naphthylalanine) (NT19). We have developed another neurotensin analog, L-[3,1'-Nal11]NT(8-13), (NT34), that exhibits a 126-fold difference in binding affinities between the rat and human receptors. This compound differs from our previous reported species-specific ligand in the steric positioning of the naphthyl ring on the L-alanine side chain.

Hsp70 mRNA induction is reduced in neurons of aged rat hippocampus after thermal stress.

Levels of heat-shock 70 mRNAs, relative to those of 18S rRNA, were quantitated in specific cell types of hippocampus of adult and aged rats subjected to identical heat shock regimens. Body temperature changes in response to the heat stress were no different in adult and aged rats. In control rats, as well as 3 h after initiation of heat shock in both adult and aged rats, relative levels of the constitutively synthesized heat-shock cognate 70 (hsc70) mRNA were highest in hippocampal neurons and much lower in glia.

Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) mice.

retinal degeneration slow (rds) is a semidominant mutation of mice with the phenotype of abnormal development of rod and cone photoreceptors, followed by their slow degeneration. The rds gene has been putatively cloned and its novel protein product initially characterized biochemically. In the present study we undertook to correct in vivo the retinal phenotype of mice with the rds mutation.