Disease relevance of UCN2

• Treatment with SCP or SRP suppressed food intake, delayed gastric emptying and decreased heat-induced edema [1].
• Expression of urocortin 2 and its inhibitory effects on intracellular ca(2+) via L-type voltage-gated calcium channels in rat pheochromocytoma (PC12) cells [2].
• Pretreatment of the cells with UCN II diminished the effects of hypoxia or Bay K8644 [3].
• The systemic administration of Ucn II decreases mean arterial pressure (arterial vascular tone) and causes tachycardia via vascular CRF2 receptor in rats, similar to the effects of Ucn I [4].
• More SRP-positive PM patients had severe proximal muscle weakness (50%) and muscle atrophy (67%) at initial presentation compared with antisynthetase-positive PM controls [5].

Psychiatry related information on UCN2

• Ucn II mRNA was increased in the parvocellular part or the magnocellular part of the hypothalamic paraventricular nucleus (PVN) following immobilization stress or 3 days of water deprivation, respectively [4].
• METHODS: Using the Heft-Parker self-assessment pain scale, 52 adults with moderate periodontitis evaluated their pain before and after SRP conducted with local anesthetic [6].

High impact information on UCN2

• It should be noted that, in all the experiments performed in which the role of SRP in cotranslational protein translocation is circumvented (Jungnickel and Rapoport, 1995; Lauring et al., 1995a, 1995b), stable translocation intermediates are allowed many minutes to establish productive interactions with the membrane [7].
• It is possible that, under these conditions, productive translocation even in the absence of NAC would require SRP [7].
• We show here that glycosylation and insertion of the asialoglycoprotein receptor into the endoplasmic reticulum membrane is cotranslational and SRP-dependent and occurs without proteolytic cleavage [8].
• Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle [9].
• These results demonstrate that one of several pathways for protein routing to the thylakoids is homologous to the SRP pathway and point to a common evolutionary origin for the protein transport systems of the endoplasmic reticulum and the thylakoid membrane [10].

Chemical compound and disease context of UCN2

• Using the structures of the E. coli Ffh/4.5S core and of the human SRP54m dimer as templates, a molecular model of the complex between human SRP RNA helix 8 and a single SRP54M molecule was constructed in which Leucine 329 was positioned in closer proximity to the RNA binding domain [11].
• METHODS: Thirty chronic periodontitis patients were randomly assigned to three groups: SRP+500 mg of systemic tetracycline twice/day for 14 days; SRP alone and SRP+tetracycline fibers (Actsite) at four selected sites for 10 days [12].
• METHOD: After baseline clinical and microbiological monitoring, 17 adult periodontitis subjects received full mouth SRP and 14 days systemic administration of either metronidazole (250 mg, TID, n=8) or amoxicillin (500 mg, TID, n=9) [13].
• CONCLUSIONS: Use of the chlorhexidine chip has significantly improved the clinical parameters of periodontitis when used as an adjunct to SRP [14].

Biological context of UCN2

• Treatment of primary human myometrial cells with UCN II to specifically activate CRH-R2 resulted in a dose-dependent increase of myosin light chain (MLC(20)) phosphorylation [15].
• 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].
• 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 [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].
• Comparative genomics of the endocrine systems in humans and chimpanzees with special reference to GNRH2 and UCN2 and their receptors [18].

Anatomical context of UCN2

• In this study we investigated the expression of urocortin II (UCN II) in human myometrium and its ability to phosphorylate intracellular components that can be involved in modulating myometrial contractility [15].
• Human endometrium expresses urocortin II and III messenger RNA and peptides [17].
• Here, we detected urocortin 2 mRNA in PC12 cells using reverse transcription-polymerase chain reaction (RT-PCR) [2].
• Urocortin 2, a new member of the corticotrophin-releasing factor (CRF) neuropeptide family, was reported to be widely expressed in the central nervous system and peripheral tissues [2].
• Physiologic data show that urocortin II, which binds selectively to CRF-R2alpha, increases the firing rate of both Purkinje cells and nuclear neurons; this response can be blocked by the CRF-R2alpha-specific antagonist, antisauvagine-30 [19].

Associations of UCN2 with chemical compounds

• Furthermore, the UCN II effect on MLC(20) was dependent on RhoA translocation to the membrane and subsequent activation of RhoA-associated kinase, as shown by the use of the specific inhibitors exoenzyme C3 and Y27632 [15].
• 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 [20].
• Urocortin 2 showed no influence on [Ca(2+)](i) in tyrode's solution containing EGTA or Ca(2+)-free tyrode's solution [2].
• Noraminophenazone blocked or diminished the action of urocortin 2 [21].
• Therefore, it is thought that Ucn II may modulate CRF and vasopressin synthesis in the PVN in a paracrine or autocrine fashion through PVN CRF2 receptor [4].

Other interactions of UCN2

• Using RT-PCR and fluorescent in situ hybridization, we demonstrated that UCN II and type-2 CRH receptor (CRH-R2) mRNAs were expressed in human nonpregnant and pregnant myometrium [15].
• 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 [22].
• 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 [22].
• Furthermore, the CRFR2-selective antagonist, astressin 2B, prevented the inhibition of estrous behavior by UCN2 and by NPY, consistent with a role for CRFR2 [23].
• Pretreatment with N/OFQ (0.25-2.0nmol/rat) did not block the effects of Ucn II and UCNIII [16].

Analytical, diagnostic and therapeutic context of UCN2

• Primary cell cultures of cerebella from embryonic day 18 mice were established, and cells were treated for either 1, 5 or 9 days with Basal Medium Eagles complete medium alone or complete medium with 1 microM CRF, urocortin, or urocortin II [24].
• The interaction of protein SRP54M from the human signal recognition particle with SRP RNA was studied by systematic site-directed mutagenesis of the RNA molecule [25].
• SRP-RNA sequence alignment and secondary structure [26].
• DESIGN: A modified Puritan-Bennett 1600 jet nebulizer was tested with a large reservoir (LR; 250 mL), medium reservoir (MR; 45 mL), and small reservoir with infusion pump (SRP; 18 mL) [27].
• Western blot analysis demonstrated that osmotic lysis of the sedimentable organelles (lutoids) in vitro caused the release of REF and SRPP from the rubber particle membrane into the cytosol [28].

References