OBJECTIVE AND DESIGN Co-localization of the four major pancreatic hormones, and also of islet amyloid polypeptide (IAPP), peptide tyrosine tyrosine (PYY), secretin and neurotensin, has been studied in the endocrine pancreas of human fetuses at 16, 18 and 22 weeks of gestation. METHODS Double and triple immunofluorescence stainings have been used. RESULTS All three fetal pancreata contained ...

Genetic correlations were found between high-affinity neurotensin receptor (NTR(H)) densities and NT-immunoreactivity (NT-ir) levels in specific brain regions and sensitivity to hypnotic and hypothermic effects of ethanol in LSXSS recombinant inbred strains of mice. Simple sequence length polymorphisms were used to identify quantitative trait loci (QTL) influencing hypnotic and hypothermic sens...

The neurotensin receptor 1 represents an important drug target involved in various diseases of the central nervous system. So far, the full exploitation of potential therapeutic activities has been compromised by the lack of compounds with favorable physicochemical and pharmacokinetic properties which efficiently penetrate the blood-brain barrier. Recent progress in the generation of stabilized...

The past few years have seen spectacular progress in the structure determination of G protein-coupled receptors (GPCRs). We now have structural representatives from classes A, B, C, and F. Within the rhodopsin-like class A, most structures belong to the α group, whereas fewer GPCR structures are available from the β, γ, and δ groups, which include peptide GPCRs such as the receptors for neurote...

Targeted theranostics is increasingly attractive in the cancer field to reduce off-target effects and provide rapid diagnosis. Neurotensin (NT) and its derivatives target neuortensin receptor 1 (NTS1) which has strong, selective, aberrant expression in certain tumour cells. This commentary briefly describes the advantages of targeting using the NT/NTS1 pairing and discusses a recent article on ...

We previously determined the structure of neurotensin receptor NTSR1 in an active-like conformation with six thermostabilizing mutations bound to the peptide agonist neurotensin. This receptor was unable to activate G proteins, indicating that the mutations restricted NTSR1 to relate agonist binding to G-protein activation. Here we analyse the effect of three of those mutations (E166A(3.49), L3...

Neurotensin (NT) and an NT-related peptide (Lys, Asn, NT; LANT-6) are produced in the chicken brain and intestine, and these peptides are encoded by the same precursor gene (NT/LANT-6 precursor). Although it has been reported that the central administration of NT suppresses food intake in mammals, the effect of NT and LANT-6 on feeding behavior in birds has not yet been investigated. In this pa...

Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3 Å crystal structure of a constitutively active, agonist-bound n...

Stress worsens certain disorders such as migraines or asthma, and has also been implicated in sudden myocardial arrest. It was previously shown that acute psychological stress by immobilization results in dura mast cell degranulation, an effect blocked by pretreatment with antiserum against corticotropin-releasing hormone (CRH). Moreover, CRH was recently shown to induce skin mast cell degranul...