PubMed Health⌕ Search

Biomedical subjects

J F Dixon

Publications and source records attributed to J F Dixon.

At least 19 recordsLinked to original sources
PubMed2000

Sexual abuse characteristics associated with survivor psychopathology.

OBJECTIVE: This study was designed to examine predictors of psychopathology in non-clinically referred, sexually abused (SA) children, ages 6-16 years, 30-60 days following abuse disclosure and termination. METHOD: Eighty SA children were administered a structured diagnostic interview and a variety of rating-scale instruments. Several forms of psychopathology were assessed, including posttraumatic stress, global functioning, anxiety, depression, and externalizing behavior. Abuse interviews also were used to guide the collection of demographic (victim age, gender) and abuse-related information (e.g., frequency of abuse). RESULTS: Abuse-related factors and demographic variables accounted for greater than half of the variance predicting global functioning, and accurately predicted posttraumatic stress disorder (PTSD) status for 86% of the participants. Also, analyses yielded significant predictors of parent-reported attention problems and sexual behavior. Of additional importance, none of the abuse-related and demographic variables predicted scores on measures of general anxiety, depression, and externalizing behavior. CONCLUSIONS: Specific demographic and sexual abuse information may, to some extent, be used to identify children who are at increased risk for short-term post-abuse psychopathology. Although the present findings suggest that such information may not be useful in the prediction of general anxiety, depression, and externalizing behavior, demographic and abuse-related variables importantly appear to account for significant variance in the prediction of global functioning, posttraumatic stress, attentiveness, and sexual behavior. Additional research is needed to improve mental health professionals' ability to identify SA children who are at high risk for psychopathology.

Adolescent↗
PubMed1999

Decline in spontaneous activity of group Aalphabeta sensory afferents after sciatic nerve axotomy in rat.

Changes are observed in the strength of central synaptic transmission and the firing behavior of primary afferents damaged by peripheral nerve injury. To clarify the relationship between synaptic strength and amount of spontaneous activity, firing behavior was studied in adult, male Sprague-Dawley rats in which sciatic nerve afferents were axotomized. Intra-axonal recordings were taken from Aalphabeta afferents within 7 h (acute, n = 309), at 3 days (n = 228), or at 10 days (n = 230) after sciatic nerve cut. The proportion of spontaneously discharging afferents fell from 22% in the acute group to < or = 13% in chronic groups. Thus, neither the progressive decline in the strength of central synaptic transmission from cut primary afferents nor the altered sensation observed after nerve cut can be explained by chronic changes in spontaneous activity of cut Aalpha/Abeta afferents.

Action Potentials↗
PubMed1998

Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex.

We previously reported that lithium stimulated extracellular glutamate accumulation in monkey and mouse cerebrocortical slices. We report here that this is caused by lithium-induced inhibition of glutamate uptake into the slice. Glutamate release was amplified 5-fold over inhibition of uptake. When the effects of lithium and the specific glutamate transporter inhibitors, L-trans-pyrrolidine-2, 4-dicarboxylic acid and dihydrokainic acid, were plotted as glutamate accumulation vs. inhibition of glutamate uptake, the plots were superimposable. This finding strongly indicates that lithium-induced glutamate accumulation is caused entirely by inhibition of uptake. With cerebrocortical synaptosomes, inhibition of glutamate uptake was greater than in slices, suggesting that presynaptic nerve endings are the primary site of inhibition of uptake by lithium. Inhibition of uptake was caused by a progressive lowering of Vmax, as the lithium concentration was increased, whereas the Km remained constant, indicating that lithium inhibited the capacity of the transporter but not its affinity. Chronic treatment of mice with lithium, achieving a blood level of 0.7 mM, which is on the low side of therapeutic, up-regulated synaptosomal uptake of glutamate. This would be expected to exert an antimanic effect. Lithium is a mood stabilizer, dampening both the manic and depressive phases of bipolar disorder. Interestingly, although the uptake of glutamate varied widely in individual control mice, uptake in lithium-treated mice was stabilized over a narrow range (variance in controls, 0.423; in lithium treated, 0.184).

Animals↗
PubMed1998

Psychopathology in non-clinically referred sexually abused children.

OBJECTIVE: To determine the prevalence of psychiatric symptoms and disorders found in non-clinically referred, sexually abused children (nCR-SAC), aged 6 to 16 years, during the 30- to 60-day period after disclosure and termination of abuse. METHOD: Eighty nCR-SAC were compared with clinical and nonclinical groups of nonabused children matched by age, race, and socioeconomic status. Structured and semistructured interviews and standardized rating scales were used for assessment. RESULTS: More posttraumatic stress disorder (PTSD) was found in the nCR-SAC than in the two comparison groups, and symptom severity was intermediate, except for symptoms of posttraumatic stress, trait anxiety, and depression, which were highest in the nCR-SAC. CONCLUSIONS: Sexually abused children are at high risk for PTSD and symptoms of posttraumatic stress, anxiety, and depression in the immediate period after disclosure and termination of abuse. Findings indicate the need for routine and systematic evaluation for these symptoms and PTSD for treatment planning.

Adolescent↗
PubMed1997

The antibipolar drug valproate mimics lithium in stimulating glutamate release and inositol 1,4,5-trisphosphate accumulation in brain cortex slices but not accumulation of inositol monophosphates and bisphosphates.

Valproic acid and lithium are effective antibipolar drugs. We recently showed that lithium stimulated the release of glutamate in monkey and mouse cerebral cortex slices, which, through activation of the N-methyl-D-aspartate receptor, increased accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. We show here that valproate behaves similarly to lithium in that at therapeutic concentrations it stimulates glutamate release and Ins(1,4,5)P3 accumulation in mouse cerebral cortex slices. The fact that these two effects are a common denominator for two structurally unrelated antibipolar drugs suggests that these effects are important in their antibipolar action. The effects of maximal concentrations of lithium and valproate on glutamate release are additive, suggesting different mechanisms for release, which are discussed. The additivity of the two drugs on glutamate release is consistent with the clinical benefit of combining the two drugs in the treatment of subsets of bipolar patients, e.g., in rapid cycling manic-depression. Unlike lithium, valproate does not increase accumulation of inositol monophosphates, inositol bisphosphates, or inositol 1,3,4-trisphosphate. This is additional evidence against the "inositol depletion" hypothesis, which states that, by trapping inositol in the form of inositol monophosphates and certain inositol polyphosphates, lithium exerts its antimanic action by inhibiting resynthesis of phosphoinositides with resultant blunting of Ins(1,4,5)P3 signaling.

Animals↗
PubMed1997

Dangling practices of 51 nurses: a pilot project.

BACKGROUND: Nurses routinely "dangle" patients to evaluate and promote tolerance to changes in body position and to determine whether the level of activity should progress. Although dangling is a widespread nursing intervention, little research has been done on it, and little is known about how nurses dangle patients. OBJECTIVE: To describe dangling practices reported by critical care and acute care nurses. METHODS: A structured interview tool, developed for the study, was used to interview 51 experienced critical care and acute nurses from seven states about dangling practices. RESULTS: Most respondents said dangling was not routinely ordered and did not require a physician's order. The nurses described numerous strategies they used beforehand to promote tolerance to dangling, for example, premedicating for pain, and multiple interventions they used if patients did not seem to do well during dangling, for example, having patients take slow, deep breaths or move the feet and arms. Indicators of intolerance to dangling included marked changes in blood pressure, heart rate, and level of consciousness and patients' comments such as, "I can't stand it." Estimates of the duration of dangling varied widely, from 1 to 10 minutes; most respondents stated that duration varied "by feel" or depended on the patient's response. The most frequently mentioned personal rule about dangling was, "Get help if you're not sure how the patient will do." CONCLUSIONS: Nurses have developed numerous approaches to dangling acutely ill patients. These approaches should be described and tested to improve nursing practice and patient outcomes.

Acute Disease↗
PubMed1996

A novel action of lithium: stimulation of glutamate release and inositol 1,4,5 trisphosphate accumulation via activation of the N-methyl D-aspartate receptor in monkey and mouse cerebral cortex slices.

Beginning at therapeutic concentrations (1-1.5mM), the anti-manic-depressive drug, lithium, stimulated the release of the major excitatory central neurotransmitter, glutamate, in monkey cerebral cortex slices in a time- and concentration-dependent manner, and this was associated with increased inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] accumulation. (+/-)-3-(2-Carboxypiperazin-4-yl)-propyl-1-phosphoric acid (CPP), dizocilpine (MK-801), ketamine, and Mg(2+)-antagonists to the N-methyl D-aspartate (NMDA) receptor/channel complex selectivity inhibited lithium-stimulated Ins(1,4,5)P3 accumulation. Antagonists to cholinergic-muscarinic, alpha 1-adrenergic, 5-HT2-serotoninergic and H1-histaminergic receptors had no effect. Antagonists to non-NMDA glutamate receptors had no effect on lithium-stimulated Ins(1,4,5)P3 accumulation. Possible reasons for this are discussed. Similar results were obtained in mouse cerebral cortex slices. Carbetapentane, which inhibits glutamate release, inhibited lithium-induced Ins(1,4,5)P3 accumulation in this model. It is concluded that the primary effect of lithium in the cerebral cortex slice model is stimulation of glutamate release, which, via activation of the NMDA receptor, leads to Ca2+ entry. Ca2+ entry, in turn, activates phospholipase C. These effects may have relevance to the therapeutic action of lithium in the treatment of manic-depression, as well as its toxic effects, especially at lithium blood levels above 1.5mM. A general conclusion which can be drawn from these studies and earlier studies in our laboratory is that lithium potentiates the action of phospholipase C, whether this enzyme is activated by lithium-induced presynaptic release of neurotransmitter, such as glutamate, or by the addition of an exogenous neurotransmitter, such as acetylcholine. However, this does not appear to be due to a direct activation of phospholipase C.

Animals↗
PubMed1994

Lithium stimulates accumulation of second-messenger inositol 1,4,5-trisphosphate and other inositol phosphates in mouse pancreatic minilobules without inositol supplementation.

Previous studies showed that lithium, beginning at therapeutic plasma concentrations in the treatment of manic depression, increased the accumulation of second-messenger inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in cerebral cortex slices of guinea pig and rhesus monkey [Lee, Dixon, Reichman, Moummi, Los and Hokin (1992) Biochem. J. 282, 377-385; Dixon, Lee, Los and Hokin (1992) J. Neurochem. 59, 2332-2335; Dixon, Los and Hokin (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 8358-8362]. These studies have now been extended to a peripheral tissue, mouse pancreatic minilobules. In the presence of carbachol, concentrations of lithium from 1 to 20 mM sharply and progressively increased the accumulation of Ins(1,4,5)P3 and inositol 1,3,4,5-tetrakisphosphate, followed by a decrease. Assay of these inositol polyphosphates by either the prelabelling technique or mass assay gave similar results. Atropine quenching of cholinergically stimulated pancreatic minilobules led to a rapid disappearance of Ins(1,4,5)P3. This disappearance was impeded by lithium. This suggested that the lithium-induced elevation in Ins(1,4,5)P3 was due to inhibition of the 5-phosphatase and, on the basis of the markedly elevated concentrations of inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] and inositol 1,4-bisphosphate in the presence of lithium, probably by feedback inhibition by these latter two compounds. An additional mechanism, i.e. a stimulatory effect of lithium on phospholipase C, cannot, however, be ruled out. The other reaction product of phospholipase C, inositol cyclic 1:2,4,5-trisphosphate, also increased in the presence of lithium. This may also be due to inhibition of the 5-phosphatase, which is the exclusive mechanism for removal of this compound. The effects of lithium on the accumulation of other inositol phosphates paralleled that of Ins(1,4,5)P3, with the exception of inositol 3,4-bisphosphate, which decreased. This was presumably due to the inhibition of Ins(1,3,4)P3 1-phosphatase by lithium. Unlike mouse cerebral cortex slices [Lee, Dixon, Reichman, Moummi, Los and Hokin (1992) Biochem. J. 282, 377-385], inositol supplementation was not required to demonstrate lithium-stimulated Ins(1,4,5)P3 accumulation in mouse pancreatic minilobules. This indicates that inositol depletion sufficient to impair lithium-stimulated Ins(1,4,5)P3 accumulation does not occur in mouse pancreatic minilobules, even though an elevation of cytidine diphosphodiacylglycerol occurred, indicating some inositol depletion due to lithium. Elevation of Ins(1,4,5)P3 by lithium may be a general phenomenon in the central nervous system and peripheral tissues under non-rate-limiting concentrations of inositol.

Animals↗
PubMed1994

Lithium stimulates glutamate "release" and inositol 1,4,5-trisphosphate accumulation via activation of the N-methyl-D-aspartate receptor in monkey and mouse cerebral cortex slices.

Beginning at therapeutic concentrations (1-1.5 mM), the anti-manic-depressive drug lithium stimulated the release of glutamate, a major excitatory neurotransmitter in the brain, in monkey cerebral cortex slices in a time- and concentration-dependent manner, and this was associated with increased inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] accumulation. (+/-)-3-(2-Carboxypiperazin-4-yl)propyl-1-phosphoric acid (CPP), dizocilpine (MK-801), ketamine, and Mg(2+)-antagonists to the N-methyl-D-aspartate (NMDA) receptor/channel complex selectively inhibited lithium-stimulated Ins(1,4,5)P3 accumulation. Antagonists to cholinergic-muscarinic, alpha 1-adrenergic, 5-hydroxytryptamine2 (serotoninergic), and H1 histaminergic receptors had no effect. Antagonists to non-NMDA glutamate receptors had no effect on lithium-stimulated Ins(1,4,5)P3 accumulation. Possible reasons for this are discussed. Similar results were obtained in mouse cerebral cortex slices. Carbetapentane, which inhibits glutamate release, inhibited lithium-induced Ins(1,4,5)P3 accumulation in this model. It is concluded that the primary effect of lithium in the cerebral cortex slice model is stimulation of glutamate release, which, presumably via activation of the NMDA receptor, leads to Ca2+ entry. Ins(1,4,5)P3 accumulation increases due to the presumed increased influx of intracellular Ca2+, which activates phospholipase C. These effects may have relevance to the therapeutic action of lithium in the treatment of manic depression as well as its toxic effects, especially at lithium blood levels above 1.5 mM.

Animals↗
PubMed1993

Inhibition of human immunodeficiency virus infection by the lectin jacalin and by a derived peptide showing a sequence similarity with gp120.

Jacalin is a plant lectin known to specifically induce the proliferation of CD4+ T lymphocytes in human. We demonstrate here that jacalin completely blocks human immunodeficiency virus type 1 (HIV-1) in vitro infection of lymphoid cells. Jacalin does not bind the viral envelope glycoprotein gp120. Besides other T cell surface molecules, it interacts with CD4, the high-affinity receptor to HIV. Binding of jacalin to CD4 does not prevent gp120-CD4 interaction and does not inhibit virus binding and syncytia formation. The anti-HIV effect of the native lectin can be reproduced by its separated alpha-subunits. More importantly, we have defined in the alpha-chain of jacalin a 14-amino acid sequence which shows high similarities with a peptide of the second conserved domain of gp120. A synthetic peptide corresponding to this similar stretch also exerts a potent anti-HIV effect. This peptide is not mitogenic for peripheral blood mononuclear cells and does not inhibit anti-CD3-induced lymphocyte proliferation. These results make jacalin alpha chain-derived peptide a potentially valuable therapeutic agent for acquired immunodeficiency syndrome.

Amino Acid Sequence↗
PubMed1992

Li+ increases accumulation of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in cholinergically stimulated brain cortex slices in guinea pig, mouse and rat. The increases require inositol supplementation in mouse and rat but not in guinea pig.

Li+, beginning at a concentration as low as 1 mM, produced a time- and dose-dependent increase in accumulation of [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4,5)P4 in acetylcholine (ACh)-stimulated guinea-pig brain cortex slices prelabelled with [3H]inositol and containing 1 mM-inositol in the final incubation period. Similar results were obtained by mass measurement of samples incubated with 10 mM-Li+ by using a receptor-binding assay, although the percentage stimulation of Ins(1,4,5)P3 accumulation by Li+ was somewhat less by this assay. The increase in accumulation of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 by Li+ was absolutely dependent on the presence of ACh. In the absence of added inositol, 1-5 mM-Li+ produced smaller increases in Ins(1,4,5)P3, but the Li(+)-dependent increase in Ins(1,3,4,5)P4 was not as affected by inositol omission. In previous studies with cholinergically stimulated rat and mouse brain cortex slices, Li+ inhibited accumulation of Ins(1,4,5)P3 in rat and inhibited Ins(1,3,4,5)P4 accumulation in rat and mouse [Batty & Nahorski (1987) Biochem. J. 247, 797-800; Whitworth & Kendall (1988) J. Neurochem. 51, 258-265]. We found that Li+ inhibited both Ins(1,4,5)P3 and Ins(1,3,4,5)P4 accumulation in these species, but we could reverse this inhibition by adding 10-30 mM-inositol; we then observed a Li(+)-induced increase in Ins(1,4,5)P3 and Ins(1,3,4,5)P4. The species differences observed in the absence of supplemented inositol were explained by the fact that a much higher concentration of inositol was required to bring the Li(+)-elevated levels of CDP-diacylglycerol (CDPDG) down to baseline in the rat and mouse. These data suggest that inositol is more rate-limiting for phosphatidylinositol synthesis in the presence of Li+ in rat and mouse, which can account for the previous reports of inhibition of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 accumulation by this ion in these species. Thus, in all species examined. Li+ could be shown to increase accumulation of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 in cholinergically stimulated brain cortex slices if the slices were supplemented with sufficient inositol to bring the Li(+)-elevated level of CDPDG down to near baseline, as seen in the absence of Li+. In guinea-pig brain cortex slices, increases in Ins(1,4,5)P3 and Ins(1,3,4,5)P4 accumulation could then be seen at Li+ concentrations as low as 1 mM, which falls within the therapeutic range of plasma concentrations in the treatment of manic-depressive disorders. These observations may have therapeutic implications.

Animals↗
PubMed1992

Agonist-stimulated inositol polyphosphate formation in cerebellum.

The accumulation of inositol polyphosphates in the cerebellum in response to agonists has not been demonstrated. Guinea pig cerebellar slices prelabeled with [3H]inositol showed the following increases in response to 1 mM serotonin: At 15 s, there was a peak in 3H label in the second messenger inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], decreasing to a lower level in about 1 min. The level of 3H label in the putative second-messenger inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] increased rapidly up to 60 s and increased slowly thereafter. The accumulation of 3H label in various inositol phosphate isomers at 10 min, when steady state was obtained, showed the following increases due to serotonin: inositol 1,3,4-trisphosphate [Ins(1,3,4)P3], eight-fold; Ins(1,3,4,5)P4, 6.4-fold; Ins(1,4,5)P3, 75%; inositol 1,4-bisphosphate [Ins(1,4)P2], 0%; inositol 3,4-bisphosphate, 100%; inositol 1-phosphate/inositol 3-phosphate, 30%; and inositol 4-phosphate, 40%. [3H]Inositol 1,3-bisphosphate was not detected in controls, but it accounted for 7.2% of the total inositol bisphosphates formed in the serotonin-stimulated samples. The fact that serotonin did not increase the formation of Ins(1,4)P2 could be due to the fact that Ins(1,4)P2 is rapidly degraded or that Ins(1,4,5)P3 is metabolized primarily by Ins(1,4,5)P3-3'kinase to form Ins(1,3,4,5)P4. In the presence of pargyline (10 microM), [3H]Ins(1,3,4,5)P4 and [3H]Ins(1,3,4)P3 levels were increased, even at 1 microM serotonin. Ketanserin (7 microM) completely inhibited the serotonin effect, indicating stimulation of serotonin2 receptors. Quisqualic acid (100 microM) also increased the levels of [3H]Ins(1,4,5)P3, [3H]Ins(1,3,4,5)P4, and [3H]Ins(1,3,4)P3, but the profile of these increases was different.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Lithium enhances accumulation of [3H]inositol radioactivity and mass of second messenger inositol 1,4,5-trisphosphate in monkey cerebral cortex slices.

We previously reported that lithium, in the presence of acetylcholine, increased accumulations of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in brain cortex slices from the guinea pig, rabbit, rat, and mouse. In the mouse and rat, the Li(+)-induced increases required supplementation of the medium with inositol. This probably relates to the following facts: (a) Brain cortices of the mouse and rat contain in vivo concentrations of inositol half of that of the guinea pig. (b) Incubated rat brain cortex slices are depleted of inositol by 80%. (c) The slices require 10 mM inositol supplementation to restore in vivo concentrations. We now show that in monkey brain cortex slices, therapeutic concentrations of Li+ increase accumulation of inositol 1,4,5-trisphosphate. The inositol 1,3,4,5-tetrakisphosphate level is not increased. Neither inositol nor an agonist is required. The same effects are seen whether inositol 1,4,5-trisphosphate is quantified by the [3H]inositol prelabeling technique or by mass assay, although mass includes a pool of inositol 1,4,5-trisphosphate that is metabolically inactive. Thus, in a therapeutically relevant model for humans, Li+ increases inositol 1,4,5-trisphosphate levels in brain cortex slices, as was previously seen in lower mammals at non-rate-limiting concentrations of inositol.

Acetylcholine↗
PubMed1991

The ABIOMED BVS 5000 system.

The ABIOMED BVS 5000 system is an investigational pulsatile biventricular assist device. Positioned externally, pneumatically driven two-chambered blood pumps can support one or both sides of the heart. A single console automatically adjusts beat rate and systolic/diastolic ratio based on compressed air flow into and out of the external system. Transthoracic cannulae connect the external system with the patient. Two patient groups are currently approved for BVS investigational use: post-cardiotomy ventricular dysfunction and post-acute myocardial infarction with cardiogenic shock. Established research protocols are followed with regard to data collection. Potential adverse effects fall into three categories: patient related, device related, and cause unknown. Weaning is initiated during cardiac recovery, and if it is successful, the pump is removed. Nursing care is based on standards of care for cardiac surgery coupled with the ABIOMED BVS 5000 nursing protocol.

Clinical Protocols↗
PubMed1990

Lymphocyte mitogenesis and CD4 modulation induced by different phorbol esters: comparative studies.

Phorbol 12-myristate 13-acetate (PMA) can stimulate T-cells via its binding to protein kinase C (PKC). Such a phenomenon occurs when a threshold of concentration as low as 1 nM of PMA is reached. Other phorbol esters possess the ability to stimulate lymphocytes but at higher thresholds of concentration. We show here that the different phorbol ester concentrations needed to induce stimulation and proliferation, estimated by both interleukin-2 receptor (IL-2R) expression and DNA synthesis, correspond very closely to those inducing the modulation of CD4 antigen, confirming a direct relationship between CD4 down-regulation and cellular activation. We estimated the structural features of these different phorbol derivatives in relation to lymphocyte activation and CD4 modulation, and confirm that the ester side chains which give to the phorbol ester derivatives their lipophilic character, discriminate, according to their length, the ability of the different compounds to reach their receptor inside the cell membrane; we also brought some evidence that the polar phorbol nucleus of these compounds is probably responsible for their interaction with the membrane receptor mainly through the hydroxyl group in the C4 position.

Adult↗
PubMed1989

The partial chemical synthesis of inositol 1,2-cyclic 4,5-trisphosphate.

Appreciable amounts of inositol 1,2-cyclic 4,5-trisphosphate (cIP3) are formed on agonist stimulation of secretory cells, e.g., pancreas (1,2) and parotid (3,4). However, the physiological role of this compound is unknown. To obtain sufficient amounts of cIP3, we have developed a synthetic method to produce cIP3 from inositol 1,4,5-trisphosphate (I(1,4,5)P3). The method is an adaptation of the dicyclohexylcarbodiimide (DCCD) method of Khorana et al. (5), which was originally developed to synthesize 2',3'-cyclic ribonucleotides. The method involves treatment of the pyridinium salt of I(1,4,5)P3 with DCCD in pyridine water, which cyclizes part of the 1-phosphate on the inositol ring to the 1,2-cyclic phosphate. The compound identified as cIP3 cochromatographed with authentic cIP3 in two HPLC systems and on ionophoresis. It was converted to I(1,4,5)P3 on mild acid treatment--a characteristic of cyclic inositol phosphates. Inositol 1,2-cyclic 4,5-trisphosphate is then purified by HPLC. Sufficient amounts of cIP3 can be prepared by this method to carry out numerous experiments on its possible cellular role.

Animals↗