Disease relevance of UCN3

• Treatment with SCP or SRP suppressed food intake, delayed gastric emptying and decreased heat-induced edema [1].
• When used at 10(-8) M they increased the amount of live cells by 25% when added prior to hypoxia, and by 20% when UCN and SCP were added at the onset of reoxygenation [2].
• CONCLUSIONS/SIGNIFICANCE: Because UCN3 is located on human chromosome 10p15.1 where quantitative trait loci for obesity have been reported, our cross species study provides further evidence that it could be proposed as a potential target for developing antiobesity drugs [3].
• Ucn and CRF receptors were all expressed in the tumor cells of pheochromocytomas, adrenocortical adenomas, and carcinomas, but its positivity was less than that in nonpathological adrenal glands, suggesting that Ucn1, Ucn3, and CRF receptors were down-regulated in these adrenal neoplasms [4].
• The RT-PCR showed expression of Ucn3 mRNA in normal portions of adrenal gland (positive ratio; 4/4), aldosterone-secreting adenomas (3/4), cortisol-secreting adenomas (1/3) and pheochromocytomas (6/7) [5].

Psychiatry related information on UCN3

• Methods: Practitioners completed a 30-item survey including demographics and religious involvement (DUREL), spirituality in patient care (SPC), and barriers (BAR) [6].

High impact information on UCN3

• Mouse urocortin III mRNA expression is found in areas of the brain including the hypothalamus, amygdala, and brainstem, but is not evident in the cerebellum, pituitary, or cerebral cortex; it is also expressed peripherally in small intestine and skin [7].
• Consistent with being the only SPC subunit with at least one intrachain disulfide bond, SPC 25 contains 4 Cys residues [8].
• AIMS: To investigate the haemodynamic, hormonal, and renal effects of peripheral urocortin 3 (Ucn3) administration for the first time in either normal health or heart failure (HF) [9].
• Immunohistochemistry in serial tissue sections with mirror images revealed that both Ucn3 and CRF2 were colocalized in more than 85% of the adrenocortical cells. mRNA in situ hybridization confirmed these findings above [4].
• CONCLUSIONS: Ucn1, Ucn3, and CRF receptors are all expressed in human adrenal cortex and medulla and may play important roles in physiological adrenal functions [4].

Chemical compound and disease context of UCN3

• Reverse phase high performance liquid chromatography showed that IR-Ucn3 in normal portions of adrenal glands and aldosterone-secreting adenomas was eluted mainly in the positions of Ucn3 and SCP with several minor peaks eluting earlier [5].
• We studied whether SPE B/SCP plays as a pathogenic factor in streptococcal infections and STSS through a histamine releasing activity [10].
• BACKGROUND & OBJECTIVES: Streptococcal pyrogenic exotoxin B/streptococcal cysteine protease (SPE B/SCP) is considered to be one of the virulence factors of Streptococcus pyogenes (S. pyogenes) which causes serious diseases such as severe invasive infections and streptococcal toxic shock syndrome (STSS) [10].

Biological context of UCN3

• Thus SCP and SRP might represent endogenous ligands for maintaining homeostasis after stress, and could allow the design of drugs to ameliorate stress-related diseases [1].
• Thus, a complete inventory of CRF family ligands and their receptors in the genomes of different organisms provides an opportunity to reveal an integrated view of the physiology and pathophysiology of the CRF/SCP family peptides, and offers new insights into the evolution of stress regulation in vertebrates [11].
• The SFD associated promoter SNPs caused a gain/loss of 12 potential transcription regulatory binding sites, while the IMCL associated coding SNPs affected the secondary structure of UCN3 mRNA [3].
• Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotropin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells [12].
• Here, we investigated the effect of intracerebroventricular (ICV) injection of 0.25, 0.75, 1.50 or 3nmol/rat of Ucn II or Ucn III on food and water intake in food deprived rats [13].

Anatomical context of UCN3

• Reverse-phase HPLC showed a broad peak of immunoreactive Ucn III eluting in the position of synthetic Ucn III in the heart, kidney, and hypothalamus [14].
• Immunocytochemistry showed positive staining of Ucn III in the myocardium and the renal tubules, particularly distal tubules [14].
• Reverse-phase HPLC of the human large intestine disclosed peaks eluting in the position of synthetic Ucn 3 or SCP [15].
• In the hypothalamus, Ucn III neurons were observed in the median preoptic nucleus and in the rostral perifornical area lateral to the paraventricular nucleus [16].
• The endometrial expression of urocortin II mRNA was significantly (P<.01) higher in the early proliferative phase of the menstrual cycle than in other phases and maternal decidua (MD), whereas that of urocortin III mRNA was higher (P<.01) in MD than in all other endometrial samples [17].

Associations of UCN3 with chemical compounds

• Ucn III secretion from the cells was measured using a highly specific RIA, and we found that high potassium, forskolin, or high glucose can stimulate Ucn III secretion from these cells [18].
• The progress of PKC inhibitors currently in clinical development, including LY333531, ISIS 3521 (CGP 64128A), bryostatin 1, GF109203x, Ro 32-0432 and Ro 31-8220, Go 6976 and Go 7611, CPR 1006, and balanol (SPC 100840) are discussed [19].
• The secreted rSPE B/SCP induced histamine release and degranulation of the human mast cell line HMC-1 [20].
• We showed that the recombinant streptococcal pyogenic exotoxin B/streptococcal cysteine protease (rSPE B/SCP) was secreted into the culture supernatant of the transformant and retained its SCP activity, which was equivalent to or greater than that of the naturally occurring molecule [20].
• This strategy of endocytic drug delivery has implications for modulating SPC protease activity needed for hormone, toxin and viral glycoprotein precursor processing in human cells [21].

Other interactions of UCN3

• More importantly, we demonstrate that SCP and SRP are able to protect cardiomyocytes even if they are administered after the hypoxic insult and prior to reoxygenation [2].
• Each of these four genes is highly conserved during evolution and the identity between mammalian and teleost orthologs ranges from >96% for CRF to >55% for SCP [11].
• Cross Species Association Examination of UCN3 and CRHR2 as Potential Pharmacological Targets for Antiobesity Drugs [3].
• Pretreatment with N/OFQ (0.25-2.0nmol/rat) did not block the effects of Ucn II and UCNIII [13].

Analytical, diagnostic and therapeutic context of UCN3

• Furthermore, SCP and SRP protect cardiomyocytes better than UCN at concentrations up to and including 10(-10) M and reduced the amount of TUNEL positive cells almost by half at concentrations of 10(-12) to 10(-10) M [2].
• RT-PCR showed expression of Ucn III mRNA in the brain, pituitary, heart, and kidney [14].
• Material eluting in the position of SCP was also found in the HPLC analysis of these tissue extracts [14].
• In the present study, we studied expression of Ucn3/SCP in the normal adrenal and adrenal tumors by radioimmunoassay and reverse transcriptase-polymerase chain reaction (RT-PCR) [5].
• OBJECTIVE: To determine the potential benefits of ISC (intermittent self-catheterisation) over SPC (supra-pubic catheterisation) in the post-operative bladder care of women following radical hysterectomy [22].

References