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At least 307 records · Page 17Linked to original sources
PubMed1993

Intraperitoneal (ip) cisplatin-mitoxantrone-interferon-alpha 2b in ovarian cancer patients with minimal residual disease.

Forty-one ovarian cancer patients with less than 2 cm residual disease after systemic cisplatin-based chemotherapy received 4 courses of an ip regimen including cisplatin (75 mg/m2), mitoxantrone (20 mg/m2), and interferon-alpha 2b (30 mil IU/m2). The most important side effects were abdominal pain and fatigue. Overall 15/41 patients (37%) required narcotic analgesia for severe abdominal pain. In 1 case laparotomy was necessary due to bowel obstruction. Grade 3-4 myelotoxicity was observed in 18/41 patients (28 courses). No treatment-related death occurred. Pathological complete response (pCR) was achieved in 23/37 (62%) evaluable patients. Four-year disease-free survival was 50%, and no relapse occurred after 32 months. The estimated 4-year progression-free survival (PFS) and overall survival were 35 and 60%, respectively. Patients who achieved pCR showed significantly better survival than the others (P < 0.000). At multivariate Cox's analysis pCR achievement was the most important predictor of PFS (P < 0.005) and survival (P < 0.02). Age (< or = 60 vs > 60) and CA-125 serum levels at entry (normal vs increased) also showed independent predictive value. On the basis of multivariate analysis results we created a risk model for survival and PFS based on age and CA-125 at entry. We identified three subgroups of patients with significantly different outcomes. With this new ip combination long-term disease-free survival is achieved in a significant part of ovarian cancer patients with small tumor burden. A longer follow-up is needed to see whether it can cure some of these patients, and further comparisons with other ip or systemic regimens are needed to draw definitive conclusions about its role in these patients.

Adult↗
PubMed2001

MaxiK channel-mediated relaxation of guinea-pig aorta following stimulation of IP receptor with beraprost via cyclic AMP-dependent and -independent mechanisms.

The present study was aimed to elucidate the cellular pathway(s) controlling vascular relaxation triggered by stimulation of prostaglandin I2 (PGI2, IP) receptor with a stable PGI2 analog, beraprost. Beraprost caused a concentration-dependent relaxation in de-endothelialized guinea-pig aorta contracted with prostaglandin F2alpha (PGF2alpha). Beraprost-induced relaxation was almost abolished in high-KCl-contracted tissue, indicating a major role of K+ conductances. In contrast to other PGI2 analogs (e.g. cicaprost and iloprost), beraprost-induced relaxation was practically abolished by a selective voltage and Ca2+-activated K+ (MaxiK, BK) channel blocker Iberiotoxin (10(-7) M) or by tetraethylammonium (2 x 10(-3) M). The relaxation induced by beraprost was not significantly affected by other K+ channel blockers glibenclamide (10(-6) M) or Ba2+ (10(-5) M), but was slightly attenuated by 4-aminopyridine (10(-4) M). Beraprost increased intracellular cyclic AMP levels, suggesting a role for cyclic AMP-dependent pathways. A selective inhibitor of cyclic AMP-specific phosphodiesterase, RO-20-1724 (10(-4) M), significantly potentiated beraprost-induced relaxation. Iberiotoxin (10(-7) M) completely counteracted this potentiation. Moreover, tension decrement due to forskolin (3 x 10(-7) M) or 8-bromo-cyclic AMP (10(-2) M) was thoroughly restored by Iberiotoxin (10(-7) M), confirming a role for a cyclic AMP-dependent mechanism. However, SQ 22,536 (10(-4) M), an adenylyl cyclase inhibitor, did not affect beraprost-induced relaxation though it almost totally inhibited the elevation of cyclic AMP contents induced by beraprost, suggesting the existence of an additional mechanism that is cyclic AMP-independent. Moreover, cholera toxin (CTX, 1 microg/ml for 6 h), which activates the stimulatory G protein of adenylyl cyclase (Gs), significantly suppressed PGF2alpha-induced contraction both in the absence and presence of SQ 22,536 (10(-4) M). Iberiotoxin (10(-7) M) was also capable of restoring the relaxation induced by CTX. These findings suggest that MaxiK channel plays a primary role in mediating smooth muscle relaxation following stimulation of IP receptor with beraprost in guinea-pig aorta. Both cyclic AMP-dependent and -independent pathways contribute to the MaxiK channel-mediated relaxation following IP receptor stimulation in this vascular tissue. Direct regulation of MaxiK channels by Gs may partly account for the cyclic AMP-independent relaxant mechanism.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2004

Juvenile hormone regulates de novo isoprenoid aggregation pheromone biosynthesis in pine bark beetles, Ips spp., through transcriptional control of HMG-CoA reductase.

Evidence is presented for transcriptional regulation of de novo pheromone biosynthesis in Ips spp. bark beetles, but the comparative biochemical and molecular approach reveals a dichotomy between species in the pini and grandicollis subgeneric groups. Radiotracer studies with 14C-acetate demonstrate that feeding on host phloem stimulates biosynthesis in males of three Ips spp. However, treatment with juvenile hormone III (JH III) stimulates biosynthesis only in Ips pini. Thus, two species in the grandicollis subgeneric group (I. grandicollis and I. paraconfusus) appear to have a different mode of regulation related to JH III than does I. pini. Between 16 and 20 hr after feeding has commenced, pheromone production, as measured by accumulation in abdominal tissue, is stimulated about 150- (I. pini) and 350-times (I. paraconfusus) above the control level of 1-10 ng/male measured at 0 hr. Treatment with JH III results in accumulation in I. pini that is 3-4 times more than in phloem-fed males, whereas the identical treatment results in only weak accumulation in I. paraconfusus (45-times less than phloem-fed males). Comparative studies of gene expression and enzyme activity related to biosynthesis also support different modes of JH III-related regulation in I. pini and I. paraconfusus. In males of both species, feeding on host phloem results in increased transcript abundance and increased activity for the key de novo isoprenoid pathway enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R). However, while JH III treatment results in comparable maximal increases in HMG-R transcript levels in both species (similar to feeding), the activity of HMG-R in crude extracts from JH III-treated male I. paraconfusus is low in comparison with male I. pini. Hypothetical explanations for the interspecific dichotomy in the regulation of pheromone biosynthesis include a second hormone or factor in grandicollis group species that functions either alone or with JH III; in both cases acting after HMG-R has been transcribed.

Animals↗
PubMed2006

Effects of magnesium sulfate administration during hypoxia on Ca(2+) influx and IP(3) receptor modification in cerebral cortical neuronal nuclei of newborn piglets.

Magnesium is a non-competitive antagonist of the NMDA receptor. Hypoxic insults to the brain are associated with a significant increase in the intranuclear Ca(2+) due to altered nuclear membrane Ca(2+) influx mechanisms including hypoxia-induced modifications of nuclear membrane IP(3) receptors. In this study we have examined the effects of magnesium sulfate administration to newborn piglets subjected to normoxia and severe hypoxia. The animals were randomly divided into normoxic (n=4), hypoxic (n=4) and magnesium sulfate treated hypoxic (n=4) groups. Hypoxia was confirmed biochemically by measuring ATP and phosphocreatine (PCr) levels in the brain tissue. Intranuclear Ca(2+) influx was assessed by measuring (45)Ca(2+) uptake. Results show a significant (P<0.05) decrease in ATP and PCr levels in hypoxic group in comparison with normoxia. On the other hand magnesium-treated hypoxic group showed a significantly (P<0.05) higher ATP and PCr in comparison with the hypoxic group. Intranuclear Ca(2+) was significantly (P<0.05) higher in the hypoxic group in comparison with both normoxic and magnesium-treated hypoxic groups. In addition results show that magnesium prevented hypoxia-induced modification of the IP(3) receptor. Magnesium treatment significantly reduced the hypoxia-induced increase in the number of receptors (reduced B(max) --P<0.05-treated hypoxia vs. hypoxia and normoxia), and reversed the receptor affinity (reduced dissociation coefficient-K(d)--P<0.05-treated hypoxia vs. normoxia). The results demonstrate that the administration of magnesium sulfate prior to hypoxia prevents the hypoxia-induced increase in intranuclear Ca(2+) and IP(3) receptor modifications. We conclude that Mg(2+ )administration prevents hypoxia-induced modification of neuronal nuclear membrane function that leads to intranuclear Ca(2+)-dependent transcription of apoptotic proteins leading to hypoxic neuronal programmed cell death.

Adenosine Triphosphate↗
PubMed1993

Real time detection of acute (IP) cocaine-enhanced dopamine and serotonin release in ventrolateral nucleus accumbens of the behaving Norway rat.

Cocaine (10 mg/kg), administered intraperitoneal (IP), was studied for its effects on dopamine (DA) and serotonin (5-HT) release in ventrolateral nucleus accumbens (vlNAcc) of conscious and behaving male, virus-free, Sprague-Dawley rats with in vivo electrochemistry (voltammetry). Miniature stearate probes detected DA and 5-HT release, on line and within a temporal resolution of seconds. Psychostimulant behaviors, in the form of four behavioral components (i.e., the classically DA-dependent behaviors of locomotor activity [ambulations], rearing, and stereotypy, and a 5-HT-ergic behavior, central ambulations) were studied concurrently with infrared photobeam detection. The results show that (IP) cocaine significantly increased vlNAcc DA release (p < 0.0001) and 5-HT release (p < 0.0012). Each of the four parameters of cocaine-induced psychostimulant behavior was concurrently and significantly increased as well (ambulations: p < 0.0001); rearing p < 0.0008; stereotypy: p < 0.0004; central ambulations: p < 0.0082). Moreover, exactly coincident data points for DA and 5-HT release occurred 10 and 40 min after (IP) cocaine administration. Cocaine-induced DA and 5-HT release were highly and positively correlated during the first hour of study (p < 0.01). As expected, increased DA release in vlNAcc after cocaine administration was significantly and positively correlated with classically DA-dependent behaviors (first- and second-hour effects) (p < 0.01) and with the 5-HT-ergic behavior, central ambulations (p < 0.01). Also, cocaine-induced 5-HT release was significantly and positively correlated with 5-HT behavior (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The Continuous Performance Test, identical pairs version (CPT-IP): I. New findings about sustained attention in normal families.

Thirty families, consisting of two parents and two adolescent children, were tested on a high-processing load Continuous Performance Test, the CPT-IP, which required identification of identical stimulus pairs within a continuously presented series of stimuli. The purpose of this study was to provide normative data for research concerned with the role of attention in psychopathology, especially schizophrenia and major affective disorder. Retest data collected from 23 of the 30 families showed the CPT-IP to be a reliable measure of attention. A major developmental effect was found in capacity to sustain attention to spatial vs. verbal stimuli, which suggested that spatial skills are most developed during childhood and adolescence, while verbal attentional skills tend to peak in adulthood. Factor analysis and family transmission patterns further suggested that the two types of attention (spatial and verbal) were independent and that each was heritable to some degree. Experimental distraction did not disrupt performance in any of the subjects and, in fact, tended to improve it in the adolescents, especially for spatial stimuli. We conclude that the CPT-IP is appropriate for use with families containing members differing widely in age and processing skills.

Adolescent↗
PubMed1992

IP-10, a gamma-interferon-inducible protein related to interleukin-8, lacks neutrophil activating properties.

IP-10, a small, gamma-interferon-inducible protein with structural homology to interleukin-8 (IL-8), was prepared by automated chemical synthesis and compared with synthetic IL-8, GRO alpha and neutrophil-activating peptide 2 (NAP-2) for neutrophil stimulating activity. The following functions were tested: cytosolic free calcium changes, chemotaxis in vitro, respiratory burst, exocytosis of azurophil and specific granules from cytochalasin B-pretreated cells, and competition for IL-8 receptor binding. At 1, 10, 100 and 1000 nM, IP-10 was inactive in all assays, in contrast to the reference peptides which exhibited the expected neutrophil stimulating effects. In addition, IP-10 did not induce neutrophil accumulation after intradermal injection in rats, and did not act as IL-8 antagonist.

Calcium↗
PubMed2004

Correlation between lifetime heterogeneity and kinetics heterogeneity during chlorophyll fluorescence induction in leaves: 1. Mono-frequency phase and modulation analysis reveals a conformational change of a PSII pigment complex during the IP thermal phase.

The relationship between the fluorescence lifetime (tau) and yield (Phi) obtained in phase and modulation fluorometry at 54 MHz during the chlorophyll fluorescence induction in dark-adapted leaves under low actinic light has been investigated. Three typical phases have been identified: (i) linear during the OI photochemical rise, (ii) convex curvature during the subsequent IP thermal rise, and (iii) linear during the PS slow decay. A similar relationship has been obtained in the fluorescence induction for the fluorescence yield measured at 685 nm plotted versus the fluorescence yield measured at 735 nm. A spectrally resolved analysis shows that the curvature of the tau-Phi relationship is not due to chlorophyll fluorescence reabsorption effects. Several other hypotheses are discussed and we conclude that the curvature of the tau-Phi relationship is due to a variable and transitory nonphotochemical quenching. We tentatively propose that this quenching results from a conformational change of a pigment-protein complex of Photosystem II core antenna during the IP phase and could explain both spectral and temporal transitory changes of the fluorescence. A variable blue shift of the 685 nm peak of the fluorescence spectrum during the IP phase has been observed, supporting this hypothesis.

Adaptation, Physiological↗
PubMed2003

Carboxyterminal cleavage of the chemokines MIG and IP-10 by gelatinase B and neutrophil collagenase.

Proteolytic processing is an important regulatory mechanism for chemokines. Matrix metalloproteinases (MMPs), such as gelatinase A/MMP-2 and gelatinase B/MMP-9, are known to process the aminoterminal end of various chemokines, including interleukin-8 (IL-8/CXCL-8) and monocyte chemotactic protein-3 (MCP-3/CXCL-7). In the present study, two proteases, gelatinase B and neutrophil collagenase/MMP-8, are shown for the first time to process the carboxyterminal end of two chemokines, monokine induced by interferon (IFN)-gamma (MIG/CXCL-9) and IFN-inducible protein-10 (IP-10/CXCL-10). Neutrophil collagenase degrades MIG into small fragments and cleaves IP-10 behind positions 71 and 73. Gelatinase B degrades IP-10 and cleaves MIG at three different sites in its extended carboxyterminal region. This results in the formation of MIG(1-94), MIG(1-93), and MIG(1-90). In general, gelatinase B was more efficient than neutrophil collagenase in processing these chemokines. Alignment of the CXC chemokines with the respective cleavage sites by both MMPs identified the ELR motif as a possible determinant for amino terminal cleavage by these MMPs.

Amino Acid Motifs↗
PubMed2005

Discovery of diphenylcarbamate derivatives as highly potent and selective IP receptor agonists: orally active prostacyclin mimetics. Part 3.

The new classes of diphenylcarbamate derivatives with a tetrahydronaphthalene skeleton as highly potent and selective IP agonists have been discovered. The optimized diphenylcarbamate type compound FK-788: (R)-4 exhibited potent antiaggregative potency with an IC50 of 18 nM and high binding affinity for the human recombinant IP receptor with K(i) values of 20 nM and selectivity for human IP over all other members of the human prostanoid receptor family. Compound (R)-4 was shown to exhibit good pharmacokinetic properties in rats and dogs, and also good bioavailability in healthy volunteers.

Administration, Oral↗
PubMed2005

Linking integrin to IP(3) signaling is important for ovulation in Caenorhabditis elegans.

Signals from germ and myoepithelial sheath cells initiate ovulation in Caenorhabditis elegans. The coordinated dilation and contraction of spermatheca lead to subsequent fertilization of oocyte. Either the dominant negative mutant pat-3 beta integrin or disruption of talin expression block ovulation. Talin loss-of-function uncovers roles in cell contractility and migration in C. elegans. Role of beta pat-3 integrins in development and function of Caenorhabditis elegans muscles and gonads, suggesting that the interaction between the cell and the extracellular matrix (ECM) is also important for ovulation. Here, we report that integrin plays an essential role in fertility via IP(3) signaling. Sterility caused by RNAi of pat-3 and ECM molecules was suppressed by increased IP(3) signaling. Our data suggest that the cell-ECM interaction controls ovulation via IP(3) signaling.

Animals↗
PubMed2004

Serum levels of a Th1 chemoattractant IP-10 and Th2 chemoattractants, TARC and MDC, are elevated in patients with systemic sclerosis.

BACKGROUND: Although abnormalities of various chemokines are detected in systemic sclerosis (SSc), there are few findings concerning Th1 or Th2 chemoattractants. OBJECTIVE: To determine whether serum levels of chemokines preferentially chemotactic for Th1 cells (IP-10 and MIG) and predominantly chemotactic for Th2 cells (TARC and MDC) are elevated and whether they correlate with clinical features in patients with SSc. METHODS: Serum samples from patients with diffuse cutaneous SSc (dSSc; n = 34), limited cutaneous SSc (lSSc; n = 30), dermatomyositis (DM; n = 15), systemic lupus erythematosus (SLE; n = 22), and normal controls (n = 30) were examined by sandwich ELISA. RESULTS: Serum TARC levels were significantly elevated in dSSc patients (P < 0.0002) and lSSc patients (P < 0.0001) compared with normal controls. Similarly, serum MDC levels were significantly increased in patients with dSSc (P < 0.02) or lSSc (P < 0.05) relative to normal controls. In addition, serum IP-10 was detected significantly more frequently in patients with dSSc (44%), lSSc (30%), or DM (53%) than normal controls (0%) and patients with SLE (0%). Furthermore, elevated TARC levels correlated with the presence of pitting scars and anti-topoisomerase I antibody, increased titers of anti-topoisomerase I and antinuclear antibody, and decreased glomerular filtration rate. Increased MDC levels were associated with pitting scars and younger ages at onset. CONCLUSION: These results suggest that both Th2 chemoattractants, TARC and MDC, and a Th1 chemoattractant IP-10 play a role in the development of SSc.

Adolescent↗
PubMed2004

Interferon-beta induces transient systemic IP-10/CXCL10 chemokine release in patients with multiple sclerosis.

Reduction of chemokine expression induced by human recombinant Interferon (IFN)-beta is thought to be a therapeutic mechanism of its action in the treatment of multiple sclerosis (MS). In vitro, IFN-beta can induce chemokine expression. Here we show that a single injection of IFN-beta induced a transient strong increase of IP-10/CXCL10 and a weak elevation of MCP-1/CCL2 plasma levels in MS patients on continuing treatment with IFN-beta. IP-10/CXCL10 bursts, which were not observed in glatiramer acetate (GA)-treated patients, correlated with occurrence of flu-like symptoms. Systemic IP-10/CXCL10 release induced by IFN-beta may influence its therapeutic effect--either negatively or positively.

Adult↗
PubMed2005

Effect of IPs, cAMP, and cGMP on the hPL and hCG secretion from human term placenta.

The acute control of human placental lactogen (hPL) and chorionic gonadotrophin (hCG) secretion by the placenta remains elusive. The in vitro release of both hormones can be stimulated by calcium inflow and by albumin. To investigate the placental secretory response to putative ligand(s) present in the maternal circulation, we evaluated the coupling of the hPL and hCG releases from term placenta with intracellular signaling pathways. Addition of NaF, forskolin or sodium nitroprusside, activators of the inositol phosphates (IPs), cAMP and cGMP pathways, significantly increased their respective messengers in villous explants but failed to affect the hPL and hCG releases from syncytiotrophoblast. By contrast, albumin did not modify the IPs, cAMP and cGMP villous content but significantly stimulated the placental hormonal release. These data suggest that the hPL and hCG secretion is not regulated through the IPs, cAMP and cGMP signaling pathways.

Chorionic Gonadotropin↗
PubMedDate not supplied

IP-10, apoptotic genes, and calcineurin subtype messenger RNA kinetics occurring in rat renal isografts from brain-dead donors.

BACKGROUND: Brain death (BD) and following ischemia/reperfusion(I/R) injury has cardinal implications in kidney transplantation (Tx). We hypothesize that inflammation, apoptosis, and drug nephrotoxicity are central mechanisms leading to initial organ damage in transplantation from BD donors. In this study, the gene kinetics of a chemokine (IP-10), an apotosis-related gene, and of calcineurin (Cn) subtype were compared using kidney isografts from BD versus living donors. METHODS: Donors were intubated and mechanically ventilated for 6 hours. Grafts were harvested 6 hours after BD, and at 1, 6, and 24 hours and 5 days after engraftment. Messenger RNA (mRNA) expression was assessed using real-time reverse transcriptase-polymerase chain reaction. RESULTS: Gene expression of IP-10 was up-regulated only among BD donor kidneys, particularly following I/R injury. These changes recovered to baseline levels thereafter. Bcl-2 was suppressed within 6 hours of BD and 1 hour after engraftment. In contrast, Bax in kidneys from BD donors was significantly up-regulated at 6 hours after engraftment. These changes were minimal in the controls. Cn Aalpha and Abeta were decreased in kidneys from BD donors before and within 1 hour after engraftment. However, these differences became insignificant thereafter. CONCLUSIONS: Marked up-regulation of IP-10 may predict the initial graft injury and the onset of delayed graft function. Apoptotic gene changes may lead kidney grafts to a preapoptotic condition and up-regulate renal toxicity caused by Cn inhibitors. This initial antigen-independent donor circumstance may be one risk factor for chronic rejection.

Animals↗
PubMed2005

CXCR3, IP-10, and Mig are required for CD4+ T cell recruitment during the DTH response to HSV-1 yet are independent of the mechanism for viral clearance.

Sensitized CD4+ T cells play an essential role in delayed type hypersensitivity (DTH) elicited by HSV-1 antigen. As activated CD4+ T cells express CXCR3, we investigated whether this chemokine receptor was involved in their recruitment. Antibody blockade of CXCR3 suppressed DTH, whereas ear pinna swelling was not impaired in mice lacking the gene for CCR5, another frequently expressed chemokine receptor. CXCR3 ligands IP-10 and Mig were elevated at the DTH site. Their neutralization significantly reduced DTH ear swelling and CD4+ T cell influx. Furthermore, CXCR3 ligand expression was abrogated and DTH diminished in mice unable to make IFN-gamma, a potent inducer of IP-10 and Mig. Interestingly, neutralization of CXCR3 or its ligands did not compromise host resistance to virus replication. Collectively, these results suggest that in the sensitized host, CXCR3, IP-10, and Mig are required for optimal DTH responsiveness but are not essential for containing HSV-1 replication in the ear pinna.

Animals↗
PubMed1983

Purification and characterization of creatine kinase, an estrogen-induced uterine protein (IP) from immature rats.

An estrogen-responsive translational product, the induced protein (IP) first described by Notides and Gorski (8), was obtained solely from the target organ, immature rat uterus, and purified to homogeneity in a procedure using two chromatography steps. The purified IP has a molecular weight of 49,000, and the isoelectric point is 5.2. Creatine kinase activity is associated with the homogeneous IP. There are some differences between the uterine enzyme and the creatine kinase BB isoenzyme, including differences in stability, and sensitivity to mercaptans. Estrogen-induced creatine kinase purified by this simple, reproducible method is a useful antigen for further studies on the translation and transcription processes involved in hormone-modulated synthesis.

Amino Acids↗
PubMed2002

Regulation of nuclear pore complex conformation by IP(3) receptor activation.

In recent years, both the molecular architecture and functional dynamics of nuclear pore complexes (NPCs) have been revealed with increasing detail. These large, supramolecular assemblages of proteins form channels that span the nuclear envelope of cells, acting as crucial regulators of nuclear import and export. From the cytoplasmic face of the nuclear envelope, nuclear pore complexes exhibit an eightfold symmetric ring structure encompassing a central lumen. The lumen often appears occupied by an additional structure alternatively referred to as the central granule, nuclear transport complex, or nuclear plug. Previous studies have suggested that the central granule may play a role in mediating calcium-dependent regulation of diffusion across the nuclear envelope for intermediate sized molecules (10-40 kDa). Using atomic force microscopy to measure the surface topography of chemically fixed Xenopus laevis oocyte nuclear envelopes, we present measurements of the relative position of the central granule within the NPC lumen under a variety of conditions known to modify nuclear Ca(2+) stores. These measurements reveal a large, approximately 9-nm displacement of the central granule toward the cytoplasmic face of the nuclear envelope under calcium depleting conditions. Additionally, activation of nuclear inositol triphosphate (IP(3)) receptors by the specific agonist, adenophostin A, results in a concentration-dependent displacement of central granule position with an EC(50) of ~1.2 nM. The displacement of the central granule within the NPC is observed on both the cytoplasmic and nucleoplasmic faces of the nuclear envelope. The displacement is blocked upon treatment with xestospongin C, a specific inhibitor of IP(3) receptor activation. These results extend previous models of NPC conformational dynamics linking central granule position to depletion of IP(3) sensitive nuclear envelope calcium stores.

Adenosine↗