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Robert T Kennedy

Publications and source records attributed to Robert T Kennedy.

At least 19 recordsLinked to original sources

Monitoring dopamine in vivo by microdialysis sampling and on-line CE-laser-induced fluorescence.

Microdialysis sampling was coupled on-line to micellar electrokinetic chromatography (MEKC) to monitor extracellular dopamine concentration in the brains of rats. Microdialysis probes were perfused at 0.3 microL/min and the dialysate mixed on-line with 6 mM naphthalene-2,3-dicarboxaldehye and 10 mM potassium cyanide pumped at 0.12 microL/min each into a reaction capillary. The reaction mixture was delivered into a flow-gated interface and separated at 90-s intervals. The MEKC separation buffer consisted of 30 mM phosphate, 6.5 mM SDS, and 2 mM HP-beta-CD at pH 7.4, and the electric field was 850 V/cm applied across a 14-cm separation distance. Analytes were detected by laser-induced fluorescence excited using the 413-nm line of a 14-mW diode-pumped laser. The detection limit for dopamine was 2 nM when sampling by dialysis. The basal dopamine concentration in dialysates collected from the striatum of anesthetized rats was 18 +/- 3 nM (n = 12). The identity of the putative dopamine peak was confirmed by showing that dopamine uptake inhibitors increased the peak and dopamine synthesis inhibitors eliminated the peak. The utility of this method for behavioral studies was demonstrated by correlating dopamine concentrations in vivo and with psychomotor behavior in freely moving rats following the intravenous administration of cocaine. Over 60 additional peaks were detected in the electropherograms, suggesting the potential for monitoring many other substances in vivo by this method.

Animals↗

Microdialysis coupled on-line to capillary liquid chromatography with tandem mass spectrometry for monitoring acetylcholine in vivo.

Capillary liquid chromatography-mass spectrometry (cLC-MS) was coupled on-line to microdialysis sampling to monitor endogenous acetylcholine (ACh) from the rodent brain. In vivo microdialysate sampled at 0.6 microL/min from the striatum of ketamine or chloral hydrate anesthetized rats was loaded onto a sample loop and then injected onto a approximately 5 cm long strong cation exchange (SCX) capillary column. A step gradient was used to separate the analyte from ionization suppressing salts contained in dialysate in 2.4 min. Sampling coupled on-line with cLC-MS allowed for high temporal resolution (data points at 2.4 min intervals), good reproducibility (10-15% relative standard deviation, R.S.D.), and sensitive limits of detection (0.04 nM or 8 amol injected). The method successfully monitored basal and stimulated levels (induced by increased K+ concentrations) of ACh from the anesthetized rat without necessitating perfusion of an acetylcholinesterase (AChE) inhibitor. Absolute and percent basal levels of ACh from rats receiving different anesthetics were also compared.

Acetylcholine↗

A capillary-PDMS hybrid chip for separations-based sensing of neurotransmitters in vivo.

A chip fabricated by multilayer soft lithography of poly(dimethylsiloxane) was created for separations-based sensing of neurotransmitters in vivo. The chip incorporated a pneumatically actuated peristaltic pump and valving system to combine low-flow push-pull perfusion sampling, on-line derivatization, and flow-gated injection onto an embedded fused-silica capillary for high speed separation of amine neurotransmitters from the brain of living animals. Six 160 microm wide by 10 microm high control channels, actuated with an overlapping 60 degrees pulse sequence, simultaneously drove sample and buffers through fluidic channels of the same dimensions. Tunable sampling flow rates of 40 to 130 nL min(-1) and separation buffer flow rates of 380 to 850 nL min(-1) were achieved with actuation frequencies between 3 and 10 Hz. On-line sampling of amine neurotransmitters with separation efficiencies in excess of 250,000 plates, detection limits of approximately 40 nM, and relative standard deviations of 4% for glutamate and aspartate were achieved in vitro. Electropherograms with resolution of gamma-aminobutyric acid, glutamine, taurine, serine, glycine, o-phosphorylethanolamine, glutamate, and aspartate could be collected every 30 s for over 4 h in vivo. It was also shown that pharmacological agents could be delivered and subsequent changes in neurotransmitter profile could be measured when delivering either 70 mM K+ artificial cerebrospinal fluid or 200 microM l-trans-pyrrolidine-2,4-dicarboxilic acid with the chip. These results demonstrate the ability of this chip to sample and monitor chemicals in the complex environment of the central nervous system with high selectivity and sensitivity over extended periods.

Animals↗

Identification and quantification of neuropeptides in brain tissue by capillary liquid chromatography coupled off-line to MALDI-TOF and MALDI-TOF/TOF-MS.

Capillary liquid chromatography (CLC) coupled off-line with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and TOF/TOF-MS were explored for identification and quantification of neuropeptides in microwave-fixed rat brain tissue. Sample was separated by gradient elution on 50-mum-inner diameter reversed-phase columns at 180 nL/min. Effluent was mixed with matrix solution and transferred to a MALDI target plate by pulsed electric field deposition, yielding sample spots with 200-300-mum diameter. Mass detection limits as low as 2 amol, corresponding to 1 pM concentration, were achieved for neuropeptides. CLC-MALDI-TOF-MS analysis of microwave-fixed rat striatum tissue yielded detection of over 400 distinctive peaks. CLC-MALDI-TOF/TOF-MS allowed identification of 10 peptides including 3 novel peptides. Quantification was evaluated using substance P as analyte and 15N3-labeled substance P as an internal standard. Quantification of substance P revealed approximately 6.8-fold higher levels than previously reported in the rat striatum. This increase is attributed to use of microwave fixation, which prevented degradation of the peptide, aggressive extraction procedures, and accounting for oxidation of substance P in the analysis. These results demonstrate that CLC-MALDI-TOF-MS is a versatile tool for neuropeptide analysis in brain tissue by allowing for detection, identification, and quantification.

Amino Acid Sequence↗

Effects of intrathecally administered nociceptin/orphanin FQ in monkeys: behavioral and mass spectrometric studies.

Nociceptin/orphanin FQ (N/OFQ) is a heptadecapeptide that is an endogenous ligand for the N/OFQ peptide (NOP) receptor. The aim of this study was to investigate the behavioral responses of N/OFQ and its major fragment N/OFQ(2-17) in monkeys following i.t. administration. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used to quantify the amounts of N/OFQ and N/OFQ(2-17) in the cerebrospinal fluid at specific time points when effects of i.t. N/OFQ were sustained and disappeared. Intrathecal administration of N/OFQ dose dependently (10-100 nmol) produced long-lasting antinociception against a noxious stimulus, 50 degrees C water, and did not elicit itch/scratching responses in monkeys. Subcutaneous pretreatment with a selective NOP receptor antagonist, (+)J-113397 [(1-[3R,4R)-1-cyclooctymethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3,-dihydro-2H-benzimidazol-2-one] (0.1 mg/kg), completely blocked i.t. N/OFQ (100 nmol)-induced antinociception. In contrast, a classic opioid receptor antagonist, naltrexone (0.01 and 1 mg/kg), failed to reverse i.t. N/OFQ-induced antinociception. MALDI-TOF-MS showed that the amount of N/OFQ(2-17) was 4-fold higher than that of N/OFQ at 1.5 h after i.t. administration of 100 nmol N/OFQ. Intrathecal N/OFQ-induced antinociception disappeared at 4.5 h, which corresponded to nearly undetectable cerebrospinal fluid levels of N/OFQ. No other metabolite of N/OFQ was detected at appreciable levels at either the 1.5- or 4.5-h time points. Although significant amounts of N/OFQ(2-17) were detected at the 1.5- and 4.5-h time points, 100 nmol N/OFQ(2-17) i.t. was inactive in changing the monkeys' nociceptive threshold. These results provide the first functional evidence of spinal N/OFQ-induced antinociception in primates and indicate that activation of spinal NOP receptors may be a potential target for spinal analgesics.

Analgesics↗

Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes.

An appropriate beta cell mass is pivotal for the maintenance of glucose homeostasis. Both insulin and IGF-1 are important in regulation of beta cell growth and function (reviewed in ref. 2). To define the roles of these hormones directly, we created a mouse model lacking functional receptors for both insulin and IGF-1 only in beta cells (betaDKO), as the hormones have overlapping mechanisms of action and activate common downstream proteins. Notably, betaDKO mice were born with a normal complement of islet cells, but 3 weeks after birth, they developed diabetes, in contrast to mild phenotypes observed in single mutants. Normoglycemic 2-week-old betaDKO mice manifest reduced beta cell mass, reduced expression of phosphorylated Akt and the transcription factor MafA, increased apoptosis in islets and severely compromised beta cell function. Analyses of compound knockouts showed a dominant role for insulin signaling in regulating beta cell mass. Together, these data provide compelling genetic evidence that insulin and IGF-I-dependent pathways are not critical for development of beta cells but that a loss of action of these hormones in beta cells leads to diabetes. We propose that therapeutic improvement of insulin and IGF-I signaling in beta cells might protect against type 2 diabetes.

Animals↗

Detection of adenylyl cyclase activity using a fluorescent ATP substrate and capillary electrophoresis.

A capillary electrophoresis laser-induced fluorescence (CE-LIF) assay was developed for detection of adenylyl cyclase (AC) activity using BODIPY FL ATP (BATP) as substrate. In the assay, BATP was incubated with AC and the resulting mixture of BATP and enzyme product (BODIPY cyclic AMP, BcAMP) separated in 5 min by CE-LIF. Substrate depletion and product accumulation were simultaneously monitored during the course of the reaction. The rate of product formation depended upon the presence of AC activators forskolin or Galpha(s)-GTPgammaS as evidenced by a more rapid BATP turnover to BcAMP compared to basal levels. The CE-LIF assay detected EC50 values for forskolin and Galpha(s)-GTPgammaS of 27 +/- 6 microM and 317 +/- 56 nM, respectively. These EC50 values compared well to those previously reported using [alpha-32P]ATP as substrate. When AC was concurrently activated with 2.5 microM forskolin and 25 nM Galpha(s)-GTPgammaS, the amount of BcAMP formed was 3.4 times higher than the additive amounts of each activator alone indicating a positively cooperative activation by these compounds in agreement with previous assays using radiolabeled substrate. Inhibition of AC activity was also demonstrated using the AC inhibitor 2'-(or-3')-O-(N-methylanthraniloyl) guanosine 5'-triphosphate with an IC50 of 9 +/- 6 nM. The use of a fluorescent substrate combined with CE separation has enabled development of a rapid and robust method for detection of AC activity that is an attractive alternative to the AC assay using radioactive nucleotide and column chromatography. In addition, the assay has potential for high-throughput screening of drugs that act at AC.

Adenosine Triphosphate↗

In vivo measurements of neurotransmitters by microdialysis sampling.

The brain contains a vast network of neurons that connect with each other at specialized junctions called synapses.A synapse consists of a presynaptic terminal (the "sending"neuron) and a postsynaptic bouton (the "receiving" neuron)that are separated by a gap of 5-50 nm (Figure 1). Chemicals released into this synaptic gap interact with receptors on the postsynaptic neuron. This leads to intracellular changes in the postsynaptic neuron-for example, an altered membrane potential or gene expression. The chemical signal is terminated by transporter proteins that transfer transmitter molecules across the membrane to the intracellular space (a process known as "reuptake")or enzymes that degrade the transmitter in the vicinity of the synapse (Figure 1). This classical view of neurotransmission might be considered point-to-point or"wired" communication because neurons communicate only with neurons to which they are specifically connected. In addition,neurotransmitters can activate receptors at more distant sites either by escaping the synapse or by being directly released into extrasynaptic space. This longer-range communication has been called "volume" transmission (1, S1; S references can be found in Supporting Information). All brain functions, from controlling movement to emotions, involve these two forms of chemical communication. Analytical chemistry has an important role to play in developing our understanding of the brain by providing tools for identification and measurement of the many chemicals involved in neurotransmission.

Brain Chemistry↗

Estradiol attenuates the K+-induced increase in extracellular GABA in rat striatum.

Estradiol acts rapidly and directly to inhibit L-type Ca2+ current in medium spiny neurons from striatum. Since medium spiny neurons contain gamma-aminobutyric acid (GABA), we hypothesized that estradiol inhibition of Ca2+ channel current in the cell body would result in decreased GABA release. In this study, we examined the effect of estradiol on the concentration of GABA, taurine, and glutamate in dialysate from striatum. In support of our hypothesis, the K+-evoked increase in GABA, but not taurine or glutamate, was significantly attenuated 30 min after treatment with estradiol.

Animals↗

Dynamic amino acid increases in the basolateral amygdala during acquisition and expression of conditioned fear.

Glutamate and gamma-aminobutyric acid (GABA) release in the amygdala are thought to be crucial for the acquisition and expression of fear memories, but the time course of amino acid changes during conditioning is unknown. We used rapid-sampling microdialysis with 14 s temporal resolution to address this issue. During auditory fear conditioning, large, rapid and transient increases in glutamate and GABA were detected, but only during the first noise-shock pairing. In contrast, rats receiving unsignaled shocks during contextual fear conditioning showed no changes in GABA and less glutamate release for the initial shock, but increased glutamate release during later shocks. Expression of conditioned fear to either a white noise or the context previously paired with shock produced similar rapid and transient increases in many amino acids in the amygdala. These experiments demonstrate glutamate and GABA levels in the amygdala are differentially modulated during auditory and contextual fear learning, and are transiently increased during the expression of fear memories.

Amino Acids↗

Microfluidic electrophoresis chip coupled to microdialysis for in vivo monitoring of amino acid neurotransmitters.

Microfluidic electrophoresis devices were coupled on-line to microdialysis for in vivo monitoring of primary amine neurotransmitters in rat brain. The devices contained a sample introduction channel for dialysate, a precolumn reactor for derivatization with o-phthaldialdehyde, a flow-gated injector, and a separation channel. Detection was performed using confocal laser-induced fluorescence. In vitro testing revealed that the initial device design had detection limits for amino acids of approximately 200 nM, relative standard deviation of peak heights of 2%, and separations within 95 s with up to 30,200 theoretical plates when applying an electric field of 370 V/cm. A second device design that allowed electric fields of 1320 V/cm to be applied while preserving the reaction time allowed separations within 20 s with up to 156,000 theoretical plates. Flow splitting into the electrokinetic network from hydrodynamic flow in the sample introduction channel was made negligible for sampling flow rates from 0.3 to 1.2 microL/min by placing a 360-microm-diameter fluidic access hole that had flow resistance (0.15-7.2) x 10(8)-fold lower than that of the electrokinetic network at the junction of the sample introduction channel and the electrokinetic network. Using serial injections, the device allowed the dialysate stream to be analyzed at 130-s intervals. In vivo monitoring was demonstrated by using the microdialysis/microfluidic device to record glutamate concentrations in the striatum of an anesthetized rat during infusion of the glutamate uptake inhibitor l-trans-pyrrolidine-2,4-dicarboxylic acid. These results prove the feasibility of using a microfabricated fluidic system coupled to sampling probes for chemical monitoring of complex media such as mammalian brain.

Amino Acids↗

Transient changes in nucleus accumbens amino acid concentrations correlate with individual responsivity to the predator fox odor 2,5-dihydro-2,4,5-trimethylthiazoline.

Predator odors elicit fear and defensive behavioral responses in rats, but a wide range of individual responsivity exists. The aim of this study was to examine whether individual differences in behavioral responsivity correlate with differences in amino acid neurotransmission to a predator fox odor, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). We investigated the time course of behaviorally evoked amino acid neurotransmitter changes in the nucleus accumbens using on-line microdialysis coupled to capillary electrophoresis with 14-s temporal resolution. One subset of animals (high responders) showed a large, biphasic increase in amino acids, such as glutamate and GABA, which lasted about 3 min. These neurochemical changes were highly correlated with increases in locomotion and burrowing, but lagged behind the behavioral changes by 2 min. A second subset of rats (low responders) showed neither behavioral activation nor changes in amino acid neurotransmission. As a positive control, rats were subjected to tail pinch, which evoked transient changes in amino acids in all animals. Cocaine (2 mg/kg, i.v.) increased locomotion but not amino acid levels. This work demonstrates that rapid and transient increases in amino acid neurotransmitters correlate with behavioral reactivity to salient stimuli.

Amino Acids↗

Microfluidic chip for low-flow push-pull perfusion sampling in vivo with on-line analysis of amino acids.

Multilayer soft lithography was used to prepare a poly(dimethylsiloxane) microfluidic chip that allows for in vivo sampling of amino acid neurotransmitters by low-flow push-pull perfusion. The chip incorporates a pneumatically actuated peristaltic pump to deliver artificial cerebrospinal fluid to a push-pull perfusion probe, pull sample from the probe, perform on-line derivatization with o-phthaldialdehyde, and push derivatized amino acids into the flow-gated injector of a high-speed capillary electrophoresis-laser-induced fluorescence instrument. Peristalsis was achieved by sequential actuation of six, 200 microm wide by 15 microm high control valves that drove fluid through three fluidic channels of equal dimensions. Electropherograms with 100,000 theoretical plates were acquired at approximately 20-s intervals. Relative standard deviations of peak heights were 4% in vitro, and detection limits for the excitatory amino acids were approximately 60 nM. For in vivo measurements, push-pull probes were implanted in the striatum of anesthetized rats and amino acid concentrations were monitored while sampling at 50 nL/min. o-Phosphorylethanolamine, glutamate, aspartate, taurine, glutamine, serine, and glycine were all detected with stable peak heights observed for over 4 h with relative standard deviations of 10% in vivo. Basal concentrations of glutamate were 1.9 +/- 0.6 microM (n = 4) in good agreement with similar methods. Monitoring of dynamic changes of neurotransmitters resulting from 10-min applications of 70 mM K(+) through the push channel of the pump was demonstrated. The combined system allows temporal resolution for multianalyte monitoring of approximately 45 s with spatial resolution 65-fold better than conventional microdialysis probe with 4-mm length. The system demonstrates the feasibility of sampling from a complex microenvironment with transfer to a microfluidic device for on-line analysis.

Amino Acids↗

Effect of intracellular delivery of energy metabolites on intracellular Ca2+ in mouse islets of Langerhans.

Regulation of glucose-induced oscillations in intracellular Ca2+ concentration ([Ca2+]i) was investigated by using a novel technique, electroporation from an electrolyte-filled capillary, to deliver energy metabolites to the intracellular compartment of mouse islets. Intracellular application of ATP resulted in a nifedipine-sensitive increase in [Ca2+]i, consistent with a KATP-channel dependent mechanism of Ca2+ influx. [Ca2+]i in islets exposed to 10 mM glucose oscillated with a period of approximately 3 min, often superimposed with faster oscillations. Electroporation of ATP blocked all types of oscillations and elevated [Ca2+]i while delivery of ADP had no effect on oscillations. Intracellular delivery of glucose-6-phosphate or fructose-1,6-bisphosphate tended to transform slow oscillations to fast oscillations. These results demonstrate that modulation of ATP concentrations and glycolytic flux are important in development of slow oscillations.

Adenine Nucleotides↗

Sample-dependent effects on the neuropeptidome detected in rat brain tissue preparations by capillary liquid chromatography with tandem mass spectrometry.

The effect of sample extraction and preparation on neuropeptidomic analysis of brain tissue by capillary liquid chromatography with tandem mass spectrometry was investigated. In agreement with previous reports, analysis of peptide extracts of brain tissue from animals sacrificed by microwave irradiation, which fixes tissue, allows identification of neuronally derived peptides whereas similar analysis of tissue from animals sacrificed without fixation does not. A comparison of a physical method for cell lysis (sonication) to physical combined with chemical cell lysis (sonication with detergent treatment) revealed that the latter method increased the number of neuronally derived peptides positively identified by approximately 3-fold, from 16 to 44, for analysis of microwave-fixed rat striatum. Use of synaptosome preparations also allowed detection of neuronally derived peptides (23 positively identified) without a requirement of microwave fixation, suggesting that this method may be a useful alternative for sample preparation. Although numerous peptides were identified in these experiments, several known neuropeptides were not detected including neuropeptide Y and neurotensin. Chemical properties such as hydrophobicity and atypical gas-phase fragmentation were found to account for the inability to detect these peptides. These results suggest that further improvement in sample preparation and automated spectral interpretation are needed to provide better coverage of neuropeptides in mammalian tissues. A total of 39 novel neuronally derived peptides, including some originating from proenkephalin and phosphatidylethanolamine binding protein, were identified in striatum and synaptosome.

Amino Acid Sequence↗

Negative mode sheathless capillary electrophoresis electrospray ionization-mass spectrometry for metabolite analysis of prokaryotes.

Capillary electrophoresis (CE) was coupled to negative mode electrospray ionisation-mass spectrometry (MS) for separation and detection of phosphorylated and acidic metabolites in extracts of prokaryotes. Unlike previous CE-MS systems for metabolite analysis, a sheathless interface was used to improve sensitivity. To accomplish this, the separation capillary was modified by creating a porous junction near the outlet where the electrospray voltage and cathodic voltage for CE were applied. The outlet of the capillary was pulled to a 5 microm inner diameter to form an electrospray emitter and had a frit fabricated near the exit to prevent clogging. During analysis pressure was applied at the inlet of the separation column to create sufficient flow towards the detector. Limits of detection for 19 metabolites in full scan mode ranged from 20 nM for ADP ribose to 2.5 microM for alpha-ketoglutarate for 40 nL injections. Extracts of Escherichia coli, strain DH5-alpha, were analyzed using this system. In full scan mode, 118 different metabolites were detected. Tandem mass spectrometry was also employed to attempt identification. Reproducible fragmentation of 19 parent peaks was found and 10 of these produced spectra that were consistent with identification obtained from matching to compounds in the MetaCyc database. These results demonstrate the utility of a sensitive CE-MS system for large scale metabolite detection in biological samples.

Electrophoresis, Capillary↗

Substrate effects on oscillations in metabolism, calcium and secretion in single mouse islets of Langerhans.

Glucose induces complex patterns of oscillations in intracellular Ca2+ concentration ([Ca2+]i), metabolism and secretion in islets of Langerhans including "slow" and "fast" pulses with period of 2-5 min and 10-20 s respectively. In an effort to elucidate the origin of slow oscillations, individual mouse islets were exposed to different fuels including glyceraldehyde, pyruvate, methyl pyruvate and alpha-ketoisocaproate (KIC), all of which bypass key steps of glycolytic metabolism, while monitoring [Ca2+]i, oxygen consumption and secretion. Glyceraldehyde gave rise to slow oscillations only when substimulatory glucose was also added to the media. Glucosamine, an inhibitor of glucokinase, blocked these slow oscillations. KIC, pyruvate, and methyl pyruvate did not give rise to slow oscillations alone or with glucose present. The addition of glucose to islets bathed in nutrient-rich cell culture media accelerated metabolism and initiated slow oscillations while glyceraldehyde did not. It is concluded that glucose has a special role in accelerating metabolism and generating slow oscillations in isolated islets of Langerhans from mice. Combined with previous observations of Ca2+ dependency for all oscillations in islets, we propose that interactions between Ca2+ influx and glycolysis are responsible for the slow oscillations. In contrast, fast oscillations can occur independent of glycolytic flux.

Animals↗

Capillary electrophoresis and fluorescence anisotropy for quantitative analysis of peptide-protein interactions using JAK2 and SH2-Bbeta as a model system.

Fluorescence anisotropy capillary electrophoresis (FACE) and affinity probe capillary electrophoresis (APCE) with laser-induced fluorescence detection were evaluated for analysis of peptide-protein interactions with rapid binding kinetics. The Src homology 2 domain of protein SH2-Bbeta (SH2-Bbeta (525-670)) and a tyrosine-phosphorylated peptide corresponding to the binding sequence of JAK2 were used as a model system. For peptide labeled with fluorescein, the K(d) = 82 +/- 7 nM as measured by fluorescence anisotropy (FA). APCE assays had a limit of detection (LOD) of 100 nM or 12 amol injected for SH2-Bbeta (525-670). The separation time of 4 s, achieved using an electric field of 2860 V/cm on 7-cm-long capillaries, was on the same time scale as complex dissociation allowing K(d) (101 +/- 12 nM in good agreement with FA measurements) and dissociation rate (k(off) = 0.95 +/- 0.02 s(-)(1) corresponding to a half-life of 0.73 s) to be determined. This measurement represents a 30-fold higher rate of complex dissociation than what had previously been measurable by nonequilibrium CE analysis of equilibrium mixtures. Using FACE, the protein was detected with an LOD of 300 nM or 7.5 fmol injected. FACE was not used for determining K(d) or k(off); however, this method provided better separation resolution for multiple forms of the protein than APCE. Both methods were found suitable for analysis of cell lysate. These results demonstrate that FACE and APCE may be useful complements to existing techniques for exploring binding interactions with rapid kinetics.

Adaptor Proteins, Signal Transducing↗