Disease relevance of Vipr2

• VPAC2 R TG mice also show increased IgE antibody responses, which mediate heightened cutaneous allergic reactions, and have depressed delayed-type hypersensitivity [1].
• Granuloma cells expressed VPAC2 mRNA [2].
• In murine schistosomiasis, granuloma T cells express VPAC2 mRNA, whereas there is none in splenocytes [2].
• Histologically, VIP and VPAC1-R agonist attenuated the severity of pancreatitis, although VPAC2-R agonist or secretin showed no significant effect [3].

High impact information on Vipr2

• We now report that mice carrying a null mutation of the VPAC(2) receptor for VIP and PACAP (Vipr2(-/-)) are incapable of sustaining normal circadian rhythms of rest/activity behavior [4].
• Critically, daily application of a VPAC(2) agonist restored rhythmicity and synchrony to VIP(-/-) SCN neurons, but not to Vipr2(-/-) neurons [5].
• Overexpression of the human VPAC2 receptor in the suprachiasmatic nucleus alters the circadian phenotype of mice [6].
• IL-4 regulates VIP receptor subtype 2 mRNA (VPAC2) expression in T cells in murine schistosomiasis [2].
• Anti-IL-4 mAb increased VPAC2 mRNA expression in Th2 cells cultured in vitro [2].

Biological context of Vipr2

• Here, we report the characterisation of the gene that encodes the mouse VPAC(2) receptor (Vipr2), localisation of the transcriptional start site and functional analysis of the promoter region [7].
• The Vipr2 gene contains 12 introns within its protein-coding region and spans 68.6 kb [7].
• The resting membrane potential in Vipr2 ( -/- ) neurones was significantly hyperpolarised as compared to WT cells (-60+/-7 vs -72+/-6 mV, p<0.01) [8].
• Activation of the VPAC2 signaling pathway induces per1 gene expression in the SCN and phase-shifts the circadian clock [9].
• Additionally, male and female VPAC2R-deficient mice presented an increased basal metabolic rate (23% and 10%, respectively) compared with their wild-type siblings [10].

Anatomical context of Vipr2

• RESULTS: Uteri from Clock(Delta19) mice show no circadian rhythm and Vipr2-/- mice show a phase-advanced rhythm compared to WT uteri [11].
• Differential signaling of T cell generation of IL-4 by wild-type and short-deletion variant of type 2 G protein-coupled receptor for vasoactive intestinal peptide (VPAC2) [12].
• WT and SD VPAC2 Th2 cell transfectants secreted equal amounts of VIP [12].
• VPAC2 R TG mice consequently have significant elevations of blood IgE, IgG1, and eosinophils [1].
• However, rIL-4 could not suppress VPAC2 mRNA expression in Th1 cells [2].

Associations of Vipr2 with chemical compounds

• By contrast, similar proportions of Vipr2-/- and wild-type SCN cells responded to gastrin-releasing peptide, arginine vasopressin or N-methyl-D-aspartate [13].
• Using a systems approach, we have developed a kinetic model integrating VPAC2 signaling mediated by the cyclic AMP (cAMP)/protein kinase A (PKA) pathway and leading to induced circadian clock gene expression [9].
• Conclusion: An efficient production procedure of a recombinant VPAC2-selective agonist with corresponding effects on glucose disposal was established [14].

Regulatory relationships of Vipr2

• Remarkably, exogenous GRP promoted SCN cellular rhythms in Vipr2(-/-) mouse slices, whereas blockade of BB2 receptors suppressed neuronal oscillations [15].
• Moreover, VIP-evoked responses from control SCN neurons were attenuated by the selective VPAC2 receptor antagonist PG 99-465 [13].
• However, granuloma cells cultured with anti-IL-4 mAb strongly expressed VPAC2 mRNA [2].
• Modeling the VPAC2-activated cAMP/PKA signaling pathway: from receptor to circadian clock gene induction [9].

Other interactions of Vipr2

• Binding and RT-PCR analyses demonstrated the presence of VPAC2 and PAC1 receptors on ES cells [16].
• Characterisation of the Mouse Vasoactive Intestinal Peptide Receptor Type 2 Gene, Vipr2, and Identification of a Polymorphic LINE-1-like Sequence That Confers Altered Promoter Activity [7].
• The VPAC2R-deficient mice showed retarded growth and had reduced serum IGF-I levels compared with gender-matched, wild-type siblings [10].
• VPAC2R-deficient mice had increased lean mass and decreased fat mass with reduced serum leptin levels [10].
• These splice variants may modify the immunoregulatory contributions of the VIP-VPAC2 axis [17].

Analytical, diagnostic and therapeutic context of Vipr2

• To address this issue, splenocytes from schistosome-infected mice were incubated with anti-CD3 to induce VPAC2 mRNA, which only appeared when cell cultures also contained anti-IL-4 mAb [2].
• In situ hybridization and immunohistochemistry demonstrated identical distributions for VPAC2 mRNA and beta-galactosidase and coexpression of the two signals in the SCN [18].
• These analyses demonstrated that activation of VPAC2R, but not VPAC1R, reduced the loss of skeletal muscle mass and force during conditions of skeletal muscle atrophy resulting from corticosteroid administration, denervation, casting-induced disuse, increased skeletal muscle mass, and force of nonatrophying muscles [19].
• In situ hybridization confirmed the presence of VPAC2 mRNA [20].
• Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that mouse ES cells express PAC1 and VPAC2 receptors [21].

References