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M J Watson

Publications and source records attributed to M J Watson.

At least 19 recordsLinked to original sources
PubMed2004

Relationship between the unbinding and main transition temperatures of phospholipid bilayers under pressure.

Using neutron diffraction and a specially constructed high pressure cell suitable for aligned multibilayer systems, we have studied, as a function of pressure, the much observed anomalous swelling regime in dimyristoyl- and dilauroyl-phosphatidylcholine bilayers, DMPC and DLPC, respectively. We have also reanalyzed data from a number of previously published experiments and have arrived at the following conclusions. (a). The power law behavior describing anomalous swelling is preserved in all PC bilayers up to a hydrostatic pressure of 240 MPa. (b). As a function of increasing pressure there is a concomitant decrease in the anomalous swelling of DMPC bilayers. (c). For PC lipids with hydrocarbon chains >or=13 carbons the theoretical unbinding transition temperature T small star, filled is coupled to the main gel-to-liquid crystalline transition temperature T(M). (d). DLPC is intrinsically different from the other lipids studied in that its T small star, filled is not coupled to T(M). (e). For DLPC bilayers we predict a hydrostatic pressure (>290 MPa) where unbinding may occur.

Binding Sites↗
PubMed2003

Could ultrasonography be used by an anaesthetist to identify a specified lumbar interspace before spinal anaesthesia?

BACKGROUND: Insertion of a needle into the lumbar subarachnoid space may cause damage to the spinal cord. Current techniques to identify a safe interspace have limitations. Ultrasound was investigated as a means to improve anatomical accuracy. METHODS: Seventeen patients attending for elective magnetic resonance imaging (MRI) of the spine were studied. Ultrasonic identification of the L3-4 interspace was attempted by an anaesthetist and a marker was placed. A radiologist identified the anatomical location of the marker on the MRI scan. RESULTS: Thirteen out of 17 markers were at the L3-4 interspace; four were at the L2-3 interspace. CONCLUSIONS: These results suggest that ultrasonography may be a useful adjunct to safe subarachnoid anaesthesia.

Adult↗
PubMed2000

A newly developed spinal simulator.

A number of studies indicate poor intra-therapist and inter-therapist reliability in the performance of graded, passive oscillatory movements to the lumbar spine. However, it has been suggested that therapists can be trained to be more consistent in their performance of these techniques if given reliable quantitative feedback. The intention of this study was to develop equipment, analogous to the lumbar spine that could be used for both teaching and research purposes. Equipment has been updated and connected to a personal IBM compatible computer. Custom designed software allows concurrent and accurate feedback to students on their performance and in a form suitable for advanced data analysis using statistical packages. The uses and implications of this equipment are discussed.

Calibration↗
PubMed2000

The Wessex Head Injury Matrix (WHIM) main scale: a preliminary report on a scale to assess and monitor patient recovery after severe head injury.

OBJECTIVE: To develop a behavioural assessment based on observations of patients recovering after severe head injury whereby data could be collected by observation and by testing everyday tasks. DESIGN: A prospective observational study of a cohort of 88 consecutive hospital admissions with severe head injury. SETTING: Two district general hospitals in the UK. PATIENTS: Eighty-eight consecutive admissions with severe traumatic head injury. Ages ranged from 14 to 67 years, mean coma duration was 14 days and mean duration of post traumatic amnesia (PTA) was 56 days. RESULTS: Fifty-eight items of behaviour were identified. Paired preference analysis was used to identify a sequence of recovery of these behaviours. The sequence began with arousal and led on to behaviours signalling recovery of social interaction and communication. Subsequent behaviours indicated increasing cognitive organization and return of orientation and memory. The behaviours on the scale are hierarchical and range from coma to emergence from PTA. CONCLUSIONS: A scale to assess patients and monitor cognitive recovery after severe head injury has been developed. While individual patients will show some departures from the sequence identified, the scale helps to make explicit the earliest stages of natural recovery patterns after head injury.

Adolescent↗
PubMed1998

Effects of nitric oxide donors, S-nitroso-L-cysteine and sodium nitroprusside, on the whole-cell and single channel currents in single myocytes of the guinea-pig proximal colon.

1. The nature of the membrane channels underlying the membrane conductance changes induced by the nitric oxide (NO) donors, S-nitroso-L-cysteine (NOCys) and sodium nitroprusside (SNP) were investigated in single myocytes isolated from the circular muscle layer of the guinea-pig proximal colon, by use of standard whole-cell and single channel recording techniques. 2. Under voltage clamp, depolarizing steps from -60 mV elicited a rapidly-developing, little-inactivating outward K+ current (IK) at potentials positive to -40 mV (at 20-25 degrees C). The steady-state level (ISS) of this K current increased in amplitude as the step potential was made to more positive potentials. If the depolarizing steps were made from a holding potential of -80 mV an additional rapidly activating and inactivating outward K+ current was also elicited, superimposed on IK. 3. At 20-25 degrees C, NOCys (2.5 microM), SNP (100 microM) and 8-bromo-cyclic GMP (500 microM) increased the amplitude of ISS of IK elicited from a holding potential of -60 mV. In contrast, NOCys (2-5 microM) had little effect on ISS at 35 degrees C. Higher concentrations (> or = 5 microM at 20-25 degrees C and > or = 10 microM at 35 degrees C) of NOCys decreased the peak amplitude (I[Peak]) and ISS of IK in a concentration-dependent manner. This blockade of IK with NOCys was always associated with an increase of the holding current (IHold), due to the activation of a membrane conductance with a reversal potential between 0 and + 30 mV and which was reduced approximately 50% upon the addition of Cd2+ (1 mM). 4. NOCys (2.5 to 10 microM) or SNP (100 microM) increased the activity of large conductance Ca2+-activated (BK) K' channels in both cell-attached and excised inside-out patches, bathed in either a symmetrical high K+ (130 mM) or an asymmetrically K+ (6 mMout: 130 mMin) physiological saline. Increases in BK channel activity in NOCys (10 microM) or SNP (100 microM) were associated with an increase in the probability of BK channel opening (N.Po), and with a negative shift of the plots of ln(N.Po) against the patch potential, with little change in the slopes of these plots. In cell-attached patches, the increase in N.Po with NOCys was often associated with a decrease in the BK single channel conductance. 5. In both cell-attached and excised patches, NOCys (2.5 to 10 microM) also activated an additional population of channels which allowed inward current flow at potentials positive to EK. In excised inside-out patches bathed in asymmetrical K+ physiological saline, these single channel currents were 2-3 pA in amplitude at -30 mV and reversed in direction near + 10 mV, even if the NaCl (126 mM) concentration in the pipette solution had been replaced with an equimolar concentration of Na gluconate. 6. Under current clamp, NOCys (2.5 microM) and SNP (100 microM) had variable effects on the membrane potential of colonic myocytes, inducing either a small membrane hyperpolarization of <5 mV, or a slowly-developing membrane depolarization of about 5 mV. In contrast, NOCys (5 microM) produced a transient membrane hyperpolarization which was followed by a large depolarization of the membrane potential to positive potentials. The electrotonic potentials elicited in response to an injection of constant hyperpolarizing current (10 pA for 400 ms) were little changed during the NOCys (5 PM)-induced membrane hyperpolarization, but significantly reduced (to 61% of control) during the periods of membrane depolarization. 7. It was concluded that NOCys and SNP, directly increased the number of active BK channels in the membrane of colonic myocytes which leads to a small rapidly oscillating membrane hyperpolarization. The following rebound depolarization in NOCys arises from both the direct opening of a population of cationic channels and the blockade of voltage- and Ca-activated K+ conductances. Finally, the apamin-sensitive K+channels underlying the initial transient hyperpolarization recorded in the intact proximal colon, in response to nerve-released or directly-applied NO, have yet to be identified at the single channel or whole-cell current level.

Animals↗
PubMed1996

Characterization of the membrane conductance changes underlying the apamin-resistant NANC inhibitory junction potential in the guinea-pig proximal and distal colon.

The nature of the electrically- or stretch-evoked nonadrenergic, noncholinergic (NANC) inhibitory junction potentials (IJPs) in circular smooth muscle cells of the guinea-pig proximal and distal colon were investigated using standard intracellular microelectrode recording techniques. We have confirmed that the NANC IJP, recorded in the presence of hyoscine (1 microM) and nifedipine (1 microM), can be divided into two components with apamin (250 nM), a blocker of the small conductance Ca2(+)-activated K+ channels. Both the apamin-sensitive and the apamin-resistant components of the IJP were blocked by tetrodotoxin (1.6 microM) or by lowering the external Ca2+ concentration (to 0.25 mM). The apamin-sensitive IJP was also blocked by omega-conotoxin GVIA (100 nM), a blocker of 'N-type' Ca2+ channels. The apamin-resistant IJP and rebound post-stimulus depolarization (PSD) were reduced upon exposure to either NG-L-arginine (NOLA), an inhibitor of nitric oxide synthase (NOS), or the nitric oxide (NO) scavenger, haemoglobin. The effects of NOLA were partially reversed in the presence of excess L-arginine, a substrate for NOS, suggesting that NO, or a related NO-donor compound, is likely to be the apamin-resistant inhibitory transmitter. Blockade of either the apamin-sensitive or apamin-resistant IJP was associated with membrane depolarization and a decrease in the membrane conductance in the absence of nerve stimulation. In the proximal colon, the apamin-resistant IJP and PSD could both be demonstrated to arise from an increase in the membrane conductance after subtraction of a non-linear background conductance. The hyperpolarization upon repetitive NANC nerve stimulation was mimicked by the NO donor, S-nitroso-L-cysteine (2.5-25 microM), which evoked a transient apamin-sensitive, but omega-conotoxin GVIA resistant, component followed by a slower apamin-resistant component. These results suggest that neurally-released NO has a number of actions in the guinea-pig colon, causing apamin-resistant hyperpolarization and depolarization, as well as directly opening apamin-sensitive K+ channels.

Animals↗
PubMed1996

Ryanodine action at calcium release channels. 2. relation to substituents of the cyclohexane ring.

Ryanodine (1) and dehydroryanodine (2) are equipotent probes for the ryanodine receptor (ryr) of calcium release channels and differ only in 9eq-methyl for 1 and 9,21-methylene for 2. Ryanoids 1 and 2 are used here to prepare novel modifications of the cyclohexane substituents to determine their effects on ryr activity and selectivity. 10-Oxo-1 when reacted with carbonyl and other reagents gave 13 C-10 derivatives including the epi-amine and epi-4-azidobenzoyl hydrazide as a candidate affinity probe. Four derivatives of 2 including the delta 8-10-hydroxy and delta 8-10-oxo compounds. Defunctionalization of the cyclohexane ring of 2 or its 4,6-ethylboronate was achieved in part by controlled periodate oxidation of the 9,21-diol to the 21-nor-9-oxo compounds. These in turn provided access to the 9ax- and 9eq-hydroxy derivatives and to the 21-nor-10-deoxy-9-oxo compound which was converted to 21-nor-10-deoxy-1 and 10-deoxy-2 along with the epimeric 10-deoxy-9-hydroxy compounds. Ryanoids of similar potency to 1 as inhibitors of [3H]-1 binding in mouse brain, rabbit skeletal muscle, and canine ventricle ryr preparations and in rat cardiac contractility assay (inhibition of mechanical response to electrical stimulation) are epi-1 and the 10-epi-amino, 10-epi-methoxyamino, and 10-epi-azidobenzoyl hydrazide derivatives and 10-deoxydehydroryanodine. With a few exceptions the potency of the ryanoids at the cardiac ryr correlates well with their inhibition of cardiac contractility, indicating that the activity is associated with stabilizing the calcium release channel in a subconducting state, thereby uncoupling the excitation-contraction process.

Animals↗
PubMed1996

Preclinical neurochemical and electrophysiological profile of 1192U90, a potential antipsychotic.

11192U90 was submitted to receptor binding and monoamine uptake assays. It bound potently at serotonin 5-HT2, dopaminergic D2, serotonin 5-HT1A, and adrenergic alpha 1 and alpha 2 receptors. It also bound to dopaminergic D1, serotonin 5-HT3, serotonin 5-HT4, and sigma sites, albeit with lower affinity. It was essentially inactive at 22 other sites, including those for cholinergic M1 and M2. It weakly inhibited uptake of 3H-norepinephrine, 3H-serotonin and 3H-dopamine. Acute doses of 1192U90 (5 and 20 mg/kg P.O.) increased whole-brain levels of dopamine metabolites but did not affect levels of norepinephrine, dopamine, and serotonin. Subcutaneous injection of 1192U90 (0.8 mg/kg/day) and clozapine (20 mg/kg/day) for 28 days preferentially decreased the number of spontaneously active dopamine cells in the ventral tegmental area (VTA) but not the substantia nigra (SN) of rats, as measured by population sampling. This outcome is characteristics of atypical antipsychotics like clozapine. Acute injections of 1192U90 reversed the rate-inhibiting effects of microiontophoretically applied dopamine and intravenously injected apomorphine and d-amphetamine on dopamine cell firing. Intravenous injection or iontophoretic application of 1192U90 or the 5-HT1A agonist (+/-)8-OH-DPAT inhibited the firing rates of dorsal raphe nucleus (DRN) neurons in rats, and the effects of both compounds were blocked by iontophoretically applied S(-) propranolol, a 5-HT1A antagonist. The results suggest that 1192U90 is a preferential dopamine D2 antagonist as well as a 5-HT1A agonist that may prove to be an atypical antipsychotic.

Amphetamine↗
PubMed1996

The short Synacthen and insulin stress tests in the assessment of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: The best dynamic test for the assessment of the hypothalamic-pituitary-adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic-pituitary-adrenal axis. DESIGN: Thirty SSTs and 27 ISTs were performed on different healthy volunteers. The results of all paired tests performed on patients in the last three years are reviewed. SETTING: Programmed Investigation Unit. SUBJECTS: Fifty-seven healthy volunteers and 166 patients. MAIN OUTCOME MEASURES: Basal serum cortisol concentration and cortisol values obtained at 30 and 60 minutes during the SST compared to the maximum obtained with adequate hypoglycemia (plasma glucose < 2 mmol/l) during an IST. RESULTS: From normal data the mean-2SD 30-minute value during the SST was 392 nmol/l and 60-minute value was 497 nmol/l. The maximal cortisol response (mean - 2SD) during the IST was 519 nmol/l. Sixty patients failed the IST, none of whom had a basal cortisol > 450 nmol/l and only six (10%) had a 30-minute cortisol value > 600 nmol/l. The 30-minute value provided a better index than the 60-minute value. The basal, 30 and 60-minute values during the SST all correlated positively and significantly with the maximal cortisol on IST. The correlations persisted for all microadenomas and macroadenomas secreting prolactin, gonadotrophins or growth hormone, patients undergoing either pre or post-adenomectomy evaluation, and in those patients who had received long-term steroids provided that the medication had been reduced and stopped two days prior to admission. CONCLUSIONS: Using a 30-minute cortisol value > 600 nmol/l as a cut-off, the short Synacthen test provides a suitable substitute for the insulin stress test. Adopting this policy will decrease the number of insulin stress tests performed by one-quarter and thus provide a substantial saving without detriment to patient care.

Adrenal Cortex Function Tests↗
PubMed1996

Effects of nitric oxide (NO) and NO donors on the membrane conductance of circular smooth muscle cells of the guinea-pig proximal colon.

1. The membrane conductance changes underlying the membrane hyperpolarizations induced by nitric oxide (NO), S-nitroso-L-cysteine (NC) and sodium nitroprusside (SNP) were investigated in the circular smooth muscle cells of the guinea-pig proximal colon, by use of standard intracellular microelectrode recording techniques. 2. NO (1%), NC (2.5-25 microM) and SNP (1-1000 microM) induced membrane hyperpolarization in a concentration-dependent manner, the hyperpolarizations to NO and NC developing more rapidly than those to SNP. The slower-developing responses to SNP were mimicked by the membrane permeable analogue of guanosine 3':5' cyclic-monophosphate (cyclic GMP), 8-bromo-cyclic GMP (500 microM), and by isoprenaline (10 microM). 3. The hyperpolarizations to NC and SNP were reduced in a low Ca2+ (0.25 mM) saline and upon the addition of haemoglobin (20 microM), but were not effected by NG-nitro-L-arginine (L-NOARG) (100 microM) or omega-conotoxin GVIA (100 nM). the hyperpolarizations to SNP were also significantly reduced by methylene blue (50 microM). 4. Apamin (250 nM) depolarized the membrane potential approximately 10 mV and reduced the initial transient component of the hyperpolarization to NO (1%) and NC (25 microM), but had no effects on the hyperpolarizations to SNP and cyclic GMP. Tetraethylammonium (TEA) (5-15 mM), had little effect on the membrane responses to NO(1%), NC(2.5-25 microM), SNP(100(-1000) microM) or cyclic GMP(500 microM). However, TEA (5-15 mM) reduced the membrane hyperpolarizations to SNP (10 microM) and isoprenaline (10 microM) in a concentration-dependent manner. The hyperpolarization to isoprenaline (10 microM) remaining in the presence of 15 mM TEA was blocked by ouabain (10 microM). 5. The amplitude of electronic potentials (1 s duration) elicited during NO donor hyperpolarizations were little changed or only slightly reduced (5-25%). However, the amplitude of the electrotonic potentials elicited during maintained electrically-induced hyperpolarizations of similar amplitude were significantly increased (30-150%), suggesting that the non-linear membrane properties of the proximal colon partially mask an increase in membrane conductance elicited during the NO donor hyperpolarizations. 6. Membrane hyperpolarization in the presence of an NO donor, 8-bromo-cyclic GMP, isoprenaline, or upon application of a maintained hyperpolarizing electrical current, often evoked oscillations of the membrane potential. These oscillations were prevented by Cs+ (1 mM). 7. These results indicate that NO and NC hyperpolarize the circular muscle of the proximal colon by activating at least two TEA-resistant membrane K+ conductances, one of which is sensitive to apamin blockade. The K+ conductance increases activated by SNP or 8-bromo-cyclic GMP were little effected by apamin, perhaps suggesting a common mechanism. In contrast, the hyperpolarization to isoprenaline appears to involve the activation of TEA-sensitive Ca2(+)-activated K+ ('BK') channels, as well as a Na:K ATPase. Finally, the 'background' membrane conductance of the circular muscle cells of the proximal colon decreased upon membrane hyperpolarization to reveal oscillations of the membrane potential which may well represent 'pacemaker' or 'slow wave' activity.

Animals↗
PubMed1994

Evaluation of 20 archival prostate tumor specimens by fluorescence in situ hybridization (FISH).

Analysis of 20 primary prostatic tumors (local Gleason grades ranging from 1 to 4) was performed on archival material obtained from formalin-fixed, paraffin-embedded blocks. Alpha satellite probes specific for the pericentric regions of chromosomes 12, 17, X, and Y were used in fluorescence in situ hybridization (FISH) assays for the examination of aneusomies for these chromosomes. Eighty percent of specimens (16/20) showed significant loss of chromosome 17 and 55% (11/20 specimens) also showed significant loss of chromosome 12; all specimens that lost chromosome 12 lost chromosome 17. Gain of the X chromosome was observed in 40% (8/20) of specimens, all but one of which also showed loss of chromosome 17. While the specimens showing gain of the X chromosome may represent polyploid cells, only one specimen also showed significant gain of chromosomes 12 and 17, suggesting that both of these chromosomes may be lost in hyperdiploid prostate cancers. Loss of the Y chromosome was not statistically significant. This study thus indicates that loss of chromosome 17 is a frequent and likely early event in prostatic cancer.

Aged↗
PubMed1992

Effects of a nitric oxide synthase inhibitor on non-cholinergic junction potentials in the circular muscle of the guinea pig ileum.

Intracellular microelectrodes were used to record junction potentials from the circular muscle cells of the guinea pig ileum in vitro at 37 degrees C in a modified Krebs solution containing nifedipine (1-2 microM) and hyoscine (1 microM). Transmural nerve stimulation, using volleys of three pulses at 50 Hz, produced a complex response consisting of an inhibitory junction potential (IJP) followed by a prolonged depolarization. Following the addition of the nitric oxide synthase inhibitor NG-nitro-L-arginine (NOLA, 100 microM) the amplitude of the IJP (recorded 10 mm aboral to the stimulating electrodes) was increased by approx. 10% (n = 4). The further addition of apamin (250 nM) abolished the IJP revealing a non-cholinergic excitatory junction potential (EJP). In other experiments (n = 8), preparations were treated with apamin then subjected to substance P desensitization (500 nM, > 20 min). Transmural nerve stimulation now produced a triphasic response (recorded 1 mm aboral to the stimulating electrodes) consisting of: (a) an initial hyperpolarization (approx. 5 mV) lasting about 1 s; followed by (b) a depolarization reaching a peak (approx. 7 mV less negative than the RMP) approx. 2 s after nerve stimulation; and finally (c) a small (approx. 3 mV) hyperpolarization. The addition of NOLA reduced all three phases by 80-90% (n = 8). The subsequent addition of L-arginine (5 mM) partially reversed these effects (n = 3). Conditioning hyperpolarization up to 20 mV increased the amplitude of the NOLA-sensitive IJP and EJP. Further conditioning hyperpolarization reduced the amplitude of the IJP and enhanced the amplitude of the EJP. Large conditioning hyperpolarizations (> 60 mV) reduced the amplitude of both the IJP and EJP. An estimation of the membrane conductance changes occurring during the initial hyperpolarization and depolarization suggest that it was either unchanged or increased. During large conditioning hyperpolarizations in the absence of nerve stimulation, the membrane potential was unstable and began to show spontaneous oscillations (up to 30 mV, every 4-5 s) resembling slow waves. These experiments indicate that NO, or a related compound, appears to mediate the nerve induced apamin-resistant IJP and substance P- and hyoscine-resistant EJP in the circular muscle of the guinea pig ileum.

Amino Acid Oxidoreductases↗
PubMed1992

Investigation of adrenal function in women with oligomenorrhoea and hirsutism (clinical PCOS) from the north-east of England using an adrenal stimulation test.

OBJECTIVE: To determine the prevalence of adrenal enzyme dysfunction in women presenting with oligomenorrhoea and hirsutism, two clinical features of polycystic ovary syndrome (PCOS). DESIGN: A prospective study of women attending outpatient clinics with these complaints. Androstenedione, dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol and cortisol were measured before and after overnight dexamethasone suppression and at 60 minutes after adrenal stimulation by ACTH injection. SUBJECTS: Fifty women with clinical features of PCOS and 37 control women with regular cycles and normal hair distribution from the catchment area of the Royal Victoria Infirmary which includes Newcastle upon Tyne, Co. Durham, Cleveland, Cumbria and Northumberland. MEASUREMENTS: Number of women with steroid responses to ACTH beyond the normal range, as defined by the responses of the control group and in previous studies. RESULTS: Nineteen women (38%) were found to have some abnormality. One woman (2%) was identified with 21-hydroxylase (21-OHase) deficiency and a second (2%) had an increase in 17-OHP compatible with the heterozygote state for 21-OHase deficiency. Four women (8%) had isolated elevations in the DHEA response consistent with minimal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency. Thirteen women (26%) showed increases in both androstenedione and DHEA, or androstenedione alone, compatible with enhanced 17-20 lyase activity. CONCLUSIONS: Twelve per cent of the group showed evidence consistent with an adrenal enzyme deficiency; 26% had results in keeping with increased adrenal androgen production without an enzyme deficiency. These findings may be of relevance both in the pathogenesis of the features of PCOS and in determining appropriate treatment for individual patients.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Sex hormones in postmenopausal HLA-identical rheumatoid arthritis discordant sibling pairs.

Dehydroepiandrosterone sulfate (DHEAS), testosterone, androstenedione, 17-beta estradiol and sex hormone binding globulin have been assayed in 50 HLA-identical postmenopausal rheumatoid arthritis (RA) discordant sibling pairs. The only difference was for DHEAS, siblings with RA having a significantly lower level than their sisters. However, in 68 patients with RA, the level of DHEAS inversely correlated with disease duration, a radiographic grading score, the Health Assessment Questionnaire score, duration of morning stiffness, and a clinical score of disease activity and severity (the Spread/Severity index). These observations, taken with that of previous work on DHEAS, suggest that low levels may be a consequence of RA rather than predisposing to the disease. The role of sex hormones in RA will have to be approached in alternative ways.

Aged↗
PubMed1991

Differential effects of omega-3 fish oils on protein kinase activities in vitro.

We studied the in vitro effects of omega-3 fish oils and other fatty acids on the activity of crude protein kinase C from S49 lymphoma cells, on partially purified enzyme from rat cerebrum, on homogeneous protein kinase C from bovine brain, and, for comparison, on type I adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. In the absence of exogenous phospholipid, the fish oils cis-5,8,11,14,17-eicosapentaenoic acid (EPA) and acid (DCHA) enhance the catalytic cis-4,7,10,13,16,19-docosahexaenoic activity of protein kinase C and support the binding of [3H]phorbol 12,13-dibutyrate, both to approximately 50% of the level supported by phosphatidylserine. In the presence of phosphatidylserine, the omega-3 fatty acids reduce catalytic activity and [3H]phorbol 12,13-dibutyrate binding by about one-half. The effects of the omega-3 fatty acids on enzyme activity suggest that fish oils act as partial agonists competitively with phosphatidylserine. EPA, DCHA, and arachidonate (but not a variety of saturated fatty acids) inhibit the cAMP-dependent protein kinase. Thus dietary fish oils and cellular fatty acids mobilized by the action of phospholipase A2 may differentially modulate the activities of protein kinase C and cAMP-dependent protein kinase. These data suggest means by which unsaturated fatty acids mobilized within cells may act as second messengers.

Animals↗