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Results for “Inositol 1,4,5-Trisphosphate Receptors”

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PubMed2018

Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder.

Bipolar disorder (BD) is a serious mood disorder associated with circadian rhythm abnormalities. Risk for BD is genetically encoded and overlaps with systems that maintain circadian rhythms. Lithium is an effective mood stabilizer treatment for BD, but only a minority of patients fully respond to monotherapy. Presently, we hypothesized that lithium-responsive BD patients (Li-R) would show characteristic differences in chronotype and cellular circadian rhythms compared to lithium non-responders (Li-NR). Selecting patients from a prospective, multi-center, clinical trial of lithium monotherapy, we examined morning vs. evening preference (chronotype) as a dimension of circadian rhythm function in 193 Li-R and Li-NR BD patients. From a subset of 59 patient donors, we measured circadian rhythms in skin fibroblasts longitudinally over 5 days using a bioluminescent reporter (Per2-luc). We then estimated circadian rhythm parameters (amplitude, period, phase) and the pharmacological effects of lithium on rhythms in cells from Li-R and Li-NR donors. Compared to Li-NRs, Li-Rs showed a difference in chronotype, with higher levels of morningness. Evening chronotype was associated with increased mood symptoms at baseline, including depression, mania, and insomnia. Cells from Li-Rs were more likely to exhibit a short circadian period, a linear relationship between period and phase, and period shortening effects of lithium. Common genetic variation in the IP3 signaling pathway may account for some of the individual differences in the effects of lithium on cellular rhythms. We conclude that circadian rhythms may influence response to lithium in maintenance treatment of BD.

Adult↗

PubMed2026

ITPRIPL1: A tumor immune-associated biomarker with prognostic and therapeutic implications in gastrointestinal cancer.

Inositol 1,4,5-trisphosphate receptor-interacting protein-like 1(ITPRIPL1) has recently been implicated in tumor-immune regulation, yet its tumor-type specificity and clinical relevance in gastrointestinal malignancies remain unclear. Here, we performed an integrative analysis of ITPRIPL1 across stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), and esophageal carcinoma (ESCA) using bulk transcriptomics, immune pathway analyses, survival modeling, single-cell RNA sequencing, immunofluorescence validation, and therapeutic correlation analyses. Although ITPRIPL1 was upregulated across gastrointestinal cancers, its prognostic significance was highly tumor-specific, with elevated expression consistently predicting unfavorable survival only in STAD. In gastric cancer, ITPRIPL1 expression was closely associated with immune-related pathways and genomic instability features, and its prognostic association varied across immune contexts, particularly according to CD8⁺/CD4⁺ T-cell abundance, with an exploratory association also observed for zeta-chain-associated protein kinase 70 (ZAP70) expression. Single-cell and immunofluorescence analyses demonstrated preferential enrichment of ITPRIPL1 in T cells and tumor-adjacent immune structures. Notably, Exploratory analyses further showed that higher ITPRIPL1 expression was associated with favorable survival outcomes in selected external pretreatment immunotherapy cohorts and with lower IC50 values for several agents in cancer cell-line pharmacogenomic datasets. Collectively, these findings identify ITPRIPL1 as an immune-associated biomarker with primary clinical relevance in gastric cancer.

Humans↗

PubMed1979

Biochemical and immunological studies on the P400 protein, a protein characteristic of the Purkinje cell from mouse and rat cerebellum.

The P400 protein is a glycoprotein of high apparent molecular weight which is abundant in isolated cerebellar Purkinje cells. On SDS polyacrylamide gels, the P400 protein reacts with 125I plant lectins such as 125I Con A. This reaction is used to increase the level of detection of the protein. The P400 protein is purified by successive extraction of synaptosomal and microsomal membranes with 2% Triton X-100 and 25% Na-cholate and preparative gel electrophoresis in SDS. The specific content of P400 protein decreases in the cerebella from homozygous nervous and Purkinje cell degeneration mutant mice, where the total number of Purkinje cells is markedly reduced, and increases in those of the reeler and weaver mice where a deficit of the granule cells exists. In the cerebellum from the homozygous staggerer mouse, a small amount of P400 protein persists. During postnatal development the specific content of P400 protein per net weight does not change up to the 12th day after birth then increases up to the 25th day when it reaches the adult level. Antisera have been raised against the purified P400 protein. They give precipitation lines by the immunodiffusion reaction of Ouchterlony against a preparation of P400 protein submitted to mild proteolytic attack. Indirect immunofluorescence performed on slices of rat cerebellum with purified anti-P400 immunoglobulin G, absorbed or not on rat cerebrum membranes, reveals that both the soma and the dendritic arborization of the Purkinje cells are labelled. The neurons from the deep cerebellar nuclei are not stained.

Animals↗

PubMed2026

Signaling mechanisms of vasopressin/oxytocin-type neuropeptide-induced muscle contraction in the sea cucumber Apostichopus japonicus.

The myoregulatory action of vasopressin/oxytocin (VP/OT)-type neuropeptides is evolutionarily conserved across Bilateria. In vertebrates, the signaling cascades involved have been comprehensively characterized in several muscle types, including uterine and gastrointestinal smooth muscles. VP/OT-type neuropeptide-induced muscle contraction or relaxation has been reported in a variety of invertebrates, but the downstream signaling pathways responsible for these effects have yet to be elucidated. Here, using heterologous cell systems and in vitro pharmacological experiments, we investigated the signaling pathways underlying VP/OT-type neuropeptide (holotocin) induced contraction of the longitudinal muscle of the body wall (LMBW) in the sea cucumber Apostichopus japonicus (phylum Echinodermata), a deuterostome invertebrate. Holotocin-induced contraction of the LMBW comprised two distinct phases: an initial rapid phasic contraction followed by a sustained tonic contraction. Pharmacological experiments revealed that upon binding to its receptor AjHOR, holotocin activates a Gαq-dependent pathway, leading to phospholipase C (PLC) activation and subsequent hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers Ca2+ release from intracellular Ca2+ stores via IP₃ receptors (IP3R), but depletion of intracellular Ca2+ does not activate store-operated Ca2+ entry (SOCE). DAG activates protein kinase C (PKC), which may modulate the activity of ion channels in the plasma membrane, resulting in membrane depolarization, opening of voltage-gated Ca2+ channels (VGCCs), and subsequent influx of extracellular Ca2+. Overall, this study reveals similarities and differences in the signaling pathways mediating smooth muscle contraction in invertebrates and vertebrates, providing new insights into the evolution of these mechanisms across the Bilateria.

Ca(2+)↗