Disease relevance of NPB

• Only when a higher dose was administered (3 nmol/100 g body weight) did NPW transiently lower blood insulin levels whereas NPB injection did not alter insulinaemia in the studied rats [1].
• Intracerebroventricular (i.c.v.) injection of NPB in mice induces hyperphagia during the first 2 h, followed by hypophagia [2].
• Mouse knockout models of the gene encoding either NPB or NPBW(1) have a gender-specific phenotype, with moderate obesity evident in males but not females [3].
• This study describes a diagnostic pitfall in the laboratory diagnosis of patients with sphingomyelinase deficiency (SMD; Niemann-Pick disease types A and B; NPA and NPB), in cases where sphingomyelinase activity was not determined with sphingomyelin as the natural enzymic substrate [4].
• This feeding- and exercise-induced stimulation of NPB is what, albeit slowly, results in muscle hypertrophy [5].

High impact information on NPB

• In situ hybridization shows distinct localizations of the prepro-NPB mRNA in mouse brain, i.e., in paraventricular hypothalamic nucleus, hippocampus, and several nuclei in midbrain and brainstem [2].
• Intracerebroventricular injection of NPB produces analgesia to s.c. formalin injection in rats [2].
• This peptide, termed neuropeptide B (NPB), has a C-6-brominated tryptophan residue at the N terminus [2].
• Cortisol response to NPB was lowered by either SQ-22536 and the protein kinase (PK) A inhibitor H-89 or U-73122 and the PKC inhibitor calphostin-C and abolished by the simultaneous exposure to H-89 and calphostin-C [6].
• NPB evoked sizable cAMP and inositol triphosphate responses from ZF/R cells, which were abrogated by the adenylate cyclase inhibitor SQ-22536 and the phospholipase C inhibitor U-73122, respectively [6].

Chemical compound and disease context of NPB

• Progressive lung infiltration is a major cause of death in Niemann-Pick disease type A and B (NPA, NPB) and in the recently defined type C2 [7].

Biological context of NPB

• Both NPB and NPW affect food intake and energy expenditure [1].
• Thus, the results suggest that NPW but not NPB exerts a potent suppressive effect on blood leptin concentrations in the rat, and this mechanism may be involved in NPW regulation of energy homeostasis [1].
• As NPB and NPW have 91% sequence homology from residues Val(13) to Leu(23), with only residue 21 differing between the two peptides, the similar C-terminal secondary structures of these two peptides are consistent with the sequences [8].
• The comprehensive cytokinesis-block micronucleus assay was used to measure micronuclei (MNi; a marker for chromosome breakage and loss), nucleoplasmic bridges (NPB; a marker of chromosome rearrangement) and nuclear buds (NBUD, a marker of gene amplification) [9].
• Mean (SD) values for oxygen uptake and heart rate during NPB for the men and women were: 19.2 (4.4) and 15.7 (3.3) ml x kg(-1) x min(-1), and 110 (10) and 122 (12) beats x min(-1), respectively, whereas the values in PB were: 48.4 (5.7) and 40.2 (4.2) ml x kg(-1) x min(-1), and 165 (12) and 172 (13) beats x min(-1), respectively [10].

Anatomical context of NPB

• Together, NPB and its receptor GPR7 exist in close proximity in the rat hypothalamus and are, hence, ideally positioned to modulate neuroendocrine functions [11].
• NPB and NPW immunoreactivities were observed in all of the cells of the pancreatic islets [1].
• Taken together, our findings indicate that NPB and NPW affect rat adrenocortical function, so they may be included in that large family of peptides involved in the autocrine-paracrine stimulation of secretion and growth of adrenal cortex [12].
• NPB did not acutely (60-min exposure) alter basal aldosterone secretion from freshly dispersed zona glomerulosa cells, while NPW raised it [12].
• The prolonged (4-day) exposure to NPW, but not NPB, raised corticosterone secretion from cultured ZF/R cells, and both neuropeptides increased the proliferation rate of cultured cells [12].

Associations of NPB with chemical compounds

• Double labeling the hypothalamic sections with NPB antiserum and vasopressin or oxytocin antibody revealed that a population of vasopressin- but not oxytocin-immunoreactive cells was irNPB [13].
• NPB also increased the blood concentration of thyroxine, and NPW that of ACTH and estradiol [14].
• The growth-stimulating effect of 10(-6) M NPB and NPW were not affected by either the PKA and PKC inhibitors H-89 and calphostin-C or the MAPK p38 antagonist SB-293580, but were abolished by both tyrphostin-23 and PD-98059 [15].
• Radioimmune assay showed that the bolus intraperitoneal injection of 2 nmol/100 g NPB or NPW raised the plasma levels of parathyroid hormone, corticosterone and testosterone [14].
• Intermittent NPB was without effect on urine flow and urinary sodium excretion but caused a significant increase in creatinine clearance [16].

Other interactions of NPB

• On the contrary, NPB injections had no effect on blood leptin and insulin concentrations [1].
• Reverse transcription-polymerase chain reaction detected the expression of NPB, NPW, GPR7-R and GPR8-like-R mRNAs in rat adrenocortical cells (both freshly-dispersed and 4-day-cultured cells) [12].
• On the contrary, when we incubated the cytokine with the albumin solution prior to the desolvation process for preparing nanoparticles (IFN-NPB), we obtained better encapsulation efficiencies (around 100%), but the cytokine was inactive: it was not detected by ELISA or bioassay in Hela cells and unable to stimulate NO production by macrophages [17].
• To achieve this objective, two different formulations were prepared by either 1) incubation between the cytokine and the newly prepared nanoparticles (IFN-NPA) or 2) between the protein and IFN-gamma prior coacervation (IFN-NPB) [17].
• A metabolic study performed with human purified 125I-alpha 2-AP (PB/NPB 7.7/2.3) showed a plasma radioactivity disappearance half-life of 72.9 h (n 60.1 +/- 5.3 h) with a normal fractional catabolic rate and a reduced absolute catabolic (synthetic) rate of 0.70 mg/kg/day (n 2.10 +/- 0.60 mg/kg/day) [18].

Analytical, diagnostic and therapeutic context of NPB

• Immunocytochemistry demonstrated the presence of NPB and NPW immunoreactivities in these same glands [14].
• The ratio of plasminogen binding (PB):non-plasminogen binding (NPB) alpha 2-AP assayed by modified crossed immunoelectrophoresis (CIE) was 7.3/2.7 (controls 6.3 +/- 0.49 SD/3.7 +/- 0.49 SD) [18].
• Intergroup comparison showed that the mean percentage of cells labeled with anti-p27K and anti-p29K was significantly higher in PB than in NPB, as seen by flow cytometry, whereas there was a higher production or accumulation of the p21K (PLP) prosomal protein in NPM than in PM, as seen by immunostaining [19].
• However, NPB was lower (-14%) in the trained gymnasts than in the control group ( P <0.05), which might be explained by a greater protein ingestion in the control group on the day of the protocol ( P <0.05) [20].

References