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Biomedical subjects

R J Walker

Publications and source records attributed to R J Walker.

At least 127 records · Page 7Linked to original sources
PubMed1994

Indomethacin potentiates exercise-induced reduction in renal hemodynamics in athletes.

Nonsteroidal anti-inflammatory drugs (NSAID) are frequently used in sports medicine but few studies have documented their potential importance in modifying exercise-induced changes in renal function. The effects of indomethacin (50 mg orally every 8 h for 36 h) on renal blood flow (RBF) and glomerular filtration rate (GFR) were investigated in eight fit healthy males (age 21-42) before and after 30-min treadmill exercise at 80% VO2max and during 120-min recovery. Each volunteer served as their own control. There were no differences between control and indomethacin for the resting values of RBF, GFR, or renal vascular resistance (RVR). Using analysis of variance for repeated measures, indomethacin produced a significant reduction in RBF compared with control (P = 0.009) that was associated with a significant elevation in RVR (P = 0.027). Changes in GFR mirrored the changes in RBF but differences failed to reach statistical significance. These results suggest that with sustained exercise indomethacin can compromise renal function and potentiate the risk of developing acute renal failure. Indomethacin and other NSAID are widely used in the sports arena, and athletes should be warned of the potential danger of their use when renal function may be compromised.

Adult↗
PubMed1994

Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy.

Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.

Animals↗
PubMed1994

The response of plasma lipoprotein (a) concentration to acute hyperinsulinemia in patients with non-insulin dependent diabetes and in healthy subjects.

The effect of acute hyperinsulinemia on plasma lipoprotein a [Lp(a)] concentration in 25 patients with non-insulin dependent diabetes mellitus (NIDDM) and in 10 healthy subjects was examined. Insulin was infused into the subjects for 2 hours while baseline plasma glucose concentrations were maintained. Plasma Lp(a) levels showed a small but significant mean (+/- SD) increase in NIDDM patients (12 +/- 26 U/l, p < 0.01) but did not vary significantly in healthy subjects (3 +/- 15 U/l) when insulin was infused. There was considerable individual variation (-35 to 98 U/l) in the response of Lp(a) to acute hyperinsulinemia and the response was correlated significantly with baseline Lp(a) levels (r = 0.399, p < 0.05). These data suggest that acute hyperinsulinemia at constant baseline glucose levels may raise plasma Lp(a) levels in NIDDM patients more particularly in those with high initial Lp(a) concentrations.

Adult↗
PubMed1993

Interaction of concanavalin A and wheat germ agglutinin with Helix acetylcholine receptors.

The effects of lectins concanavalin A (Con A) and wheat germ agglutinin (WGA), were studied on acetylcholine (ACh) responses of physically isolated internally dialyzed Helix aspersa neurons using the concentration clamp method and on the binding of [3H]alpha-bungarotoxin to the cluster of neurons. Con A and WGA have different simple sugar specificity and produced different actions on ACh-evoked Cl conductance responses, which were antagonized by Con A (5 micrograms/ml) but were not altered by WGA. Con A depressed ACh responses when applied extracellularly while it had no effect on ACh responses of the same neuron when added to the intracellular solution, thus indicating that Con A specific glycoproteins are exposed on the surface of the neuron. The studies of the effect of Con A on the properties of the ACh binding site (receptor) have demonstrated, that (1) the onset of desensitization of ACh responses of the dialyzed neurons, determined from the decay of ACh-current from peak to plateau in the continued presence of agonist and best fitted by a double exponential function, was accelerated by Con A; (2) Con A depressed the maximal ACh induced current in a dose response relationship and altered the Hill coefficients; (3) Con A depressed the binding of [3H]alpha-bungarotoxin to the cluster of neurons. These results indicate that Con A receptors on the surface of the neuronal membrane play a regulatory role in the ACh-receptor system and suggest that binding of lectin molecules to their receptors leads to inhibition of binding of ACh to ACh-receptors and to acceleration of the kinetics of desensitization of ACh receptors. All the effects of Con A, that is, on the peak amplitude, desensitization, dose-response relationship of ACh induced current and binding of [3H]alpha-bungarotoxin, could be recovered by D-mannose, a competitive inhibitor of Con A binding to its receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

5-Hydroxytryptamine and motility in Fasciola hepatica.

The study motility in Fasciola has been practically very difficult. 5-Hydroxytryptamine (5-HT) has a strong stimulatory action on Fasciola movement, increasing both the amplitude and frequency of contractions, but most of the evidence for a transmitter role of 5-HT at the neuromuscular junction comes from fairly elementary pharmacological and neurochemical studies. As discussed here by Lindy Holden-Dye and Robert Walker, it still remains to be established that the effect of 5-HT on motility is mediated by 5-HT receptors actually present on the muscle cells. Analysis of the transmitter role of 5-HT and the delineation of the receptor type(s) involved in its stimulatory action will require the application of molecular techniques such as patch clamping of muscle cells, and cloning, sequencing and expression of 5-HT receptor complementary DNAs.

Journal Article↗
PubMed1993

The actions of RFamide neuroactive peptides on the isolated heart of the giant African snail, Achatina fulica.

1. The effects of a range of RFamide peptides were examined on the frequency, amplitude and tone of the isolated heart of Achatina fulica. 2. FMRFamide, FLRFamide and SDPNFLRFamide were potent excitants while LPLRFamide, KHEYLRFamide and GSFFRFamide were weak excitants. 3. DNFLRFamide and SSLFRFamide were potent inhibitory peptides while LFRFamide, GSLFRFamide and KNEFIRFamide were weak inhibitory peptides. 4. MRFamide, LRFamide and RFamide were inactive. 5. It is concluded that a tetrapeptide sequence is the minimal requirement for activity on the Achatina heart. With the exceptions of DNFLRFamide and in most preparations GSFFRFamide, LRFamide peptides are excitatory while FRFamide peptides are inhibitory. 6. Due to its inhibitory effect and high potency, the sequence DNFLRFamide warrants further investigation.

Amino Acid Sequence↗
PubMed1993

Physiological and pharmacological studies on annelid and nematode body wall muscle.

1. This review covers the pharmacology and physiology of the body wall muscle systems of nematodes and annelids. 2. Both acetylcholine and gamma-aminobutyric acid (GABA) play important roles in the control of body wall muscle in both phyla. In annelids and nematodes, acetylcholine is the excitatory neuromuscular transmitter while GABA is the inhibitory neuromuscular transmitter. In addition, 5-hydroxytryptamine (5-HT) has a modulatory role at annelid body wall muscle but little if any effect on nematode body wall muscle. 3. The acetylcholine receptor of the body wall muscle can be classified as nicotinic-like in both phyla though the annelid receptor has not been analysed in detail. In nematodes, vertebrate ganglionic nicotinic agonists were the most effective of those so far examined while mecamylamine and benzoquinonium were the most effective antagonists. Both neuronal bungarotoxin and neosurugatoxin were potent antagonists of acetylcholine excitation at the nematode receptor. 4. The GABA receptor of the body wall muscle exhibits similarities with the vertebrate GABA-A receptor in both phyla. Picrotoxin is a very weak or inactive antagonist at leech and nematode GABA receptors, while bicuculline methiodide blocks leech GABA receptors but is inactive on nematode GABA receptors. Picrotoxin does block GABA responses of earthworm body wall muscle. All these GABA responses are chloride mediated. 5. Neuroactive peptides of the RFamide family occur in both phyla and FMRFamide has been identified in leeches. RFamides probably have an important role in heart regulation in leeches and in modulation of their body wall muscles. RFamides also modulate nematode body wall muscle activity with KNEFIRFamide raising muscle tone while SDPNFLRFamide relaxes the muscle. It is likely that this family and other neuroactive peptides play an important role in the physiology of body wall muscle throughout both phyla.

Amino Acid Sequence↗
PubMed1993

An ion-sensitive microelectrode study on the effect of a high concentration of ivermectin on chloride balance in the somatic muscle bag cells of Ascaris suum.

Ivermectin has been shown to increase chloride conductances of invertebrate cells. On the muscle cells of the parasitic nematode Ascaris, ivermectin acts as both a GABA receptor antagonist and a chloride channel opener. In this study, ion-sensitive microelectrodes were used to investigate the effect of ivermectin on intracellular Cl- concentration of the somatic muscle bag cells of Ascaris suum. Incubation of muscle cells with ivermectin (10 microM in 1% dimethyl sulphoxide vehicle for 60 min) increased intracellular Cl- by 2.9 mM or 15% compared to controls (P < 0.01, n = 6).

Animals↗
PubMed1993

Pharmacological profile of the 5-hydroxytryptamine receptor of Fasciola hepatica body wall muscle.

5-HT is a candidate for the excitatory transmitter at the neuromuscular junction in trematodes including Fasciola hepatica. This study has determined the response of a muscle strip preparation from Fasciola hepatica to 5-HT and a range of agonists that distinguish between the vertebrate receptor 5-HT subtypes. 5-HT increased the resting tone and the rhythmic activity of the muscle strip. Of the 19 compounds tested, only 10 had an effect similar to 5-HT and all but 2 of these were tryptamine compounds. 5-HT was more potent than tryptamine whilst 4-OH-tryptamine had no effect, suggesting that the response is mediated by a 5-HT rather than a tryptamine receptor. 5-Fluorotryptamine and 5-carboxyamidotryptamine were the most potent agonists. 8-OH-DPAT also mimicked the effect of 5-HT, though less potently. Assuming that these agents elicit their response through a common receptor, this suggests the presence of a 5-HT receptor with similar properties in terms of agonist recognition as the vertebrate 5-HT1 class of receptor involved in controlling Fasciola muscle motility.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

A comparison between enalapril and captopril on insulin sensitivity in normotensive healthy volunteers.

BACKGROUND: Captopril has been shown to improve insulin sensitivity in insulin resistant hypertensive individuals and enalapril has been shown to improve insulin sensitivity in a small group of healthy volunteers, but there has been no direct comparison of the effects of the different angiotensin converting enzyme inhibitors (ACEIs) on insulin sensitivity in either insulin sensitive or insulin insensitive populations. AIM: To compare the impact of two different ACEIs (captopril and enalapril) on insulin mediated glucose uptake in normotensive, non-obese, insulin sensitive subjects. METHOD: A single blind cross-over study comparing captopril (6.25 mg twice daily) and enalapril (5 mg once daily) for 28 days with a 28 day washout period between drugs. Insulin mediated glucose uptake was measured by means of the euglycaemic hyperinsulinaemic clamp at the start and completion of each period of drug therapy. RESULTS: Both drugs resulted in elevations of fasting insulin levels (mean difference +/- SEM for combined data, 2.7 +/- 1.8; p < 0.05) and a reduction in insulin mediated glucose uptake (mean difference for combined data, -0.72 +/- 0.37 mg/kg-1 minute-1; p = 0.056). Results were similar for both agents and suggest a class effect. CONCLUSIONS: The increase in fasting insulin levels, and reduction in insulin mediated glucose uptake in this study are in contrast to findings in obese and hypertensive subjects, and indicate that studies of insulin sensitivity of ACEIs in non-obese, normotensive subjects are inappropriate for predicting likely effects in clinical practice.

Adult↗
PubMed1992

Effects of RU33368, a low affinity ligand for neuronal benzodiazepine receptors, on rodent behaviours and GABA-mediated synaptic transmission in rat cerebellar slices.

1. The effects of the low affinity benzodiazepine receptor ligand RU33368 were studied on rodent behaviours and on GABA-mediated synaptic transmission in rat cerebellar slices. 2. RU33368 inhibited stress induced ultrasounds in rat pups without inducing marked muscle relaxation. RU33368 also enhanced operant responding in rats that had been suppressed by mild footshock. These effects of RU33368 in these two models of anxiety were both blocked by the benzodiazepine antagonist Ro15-1788 (flumazonil). 3. In cerebellar slices RU33368 enhanced stimulus-induced synaptic inhibition of Purkinje layer cells with a minimal effective concentration in the order of 1 microM. The classical benzodiazepine agonist RU32007 was approx. 10 times more potent. This action of RU33368 was blocked by Ro15-1788. 4. The minimal effective concentration of RU33368 fully blocked the effect of RU32007 in 2 of 4 cells tested and partially antagonized it in a third cell. 5. These data suggest that RU33368 is a partial agonist at benzodiazepine receptors and this, at least in part, explains its non-sedative anxiolytic behavioural profile.

Animals↗
PubMed1992

Actions of APGW-amide and GW-amide on identified central neurons of the snail, Helix aspersa.

1. Actions of APGWamide and GWamide have been examined on identified central neurons of the snail, Helix aspersa. 2. In F1 neurons, both APGWamide and GWamide, 0.5-5 microM, reversibly inhibited the amplitude of evoked-IPSPs which were dopaminergic, but had no direct effect on membrane potential, cell firing rate, or dopamine-induced responses. These results indicate that the actions of APGWamide and GWamide in F1 neurons are at presynaptic sites. 3. At concentrations between 0.5 and 10 microM, APGWamide and GWamide had direct postsynaptic effects on F2 neurons. They inhibited the spike activity and hyperpolarized the membrane potential of F2 neurons in a dose-dependent manner with a reversal potential around -85 mV which is close to Ek. 4. In K+ free solution, the inhibitory effects of APGWamide and GWamide were potentiated, while they were reduced by increasing external K+ concentration. Either tetraethylammonium (10 mM) or 4-aminopyridine (500 microM) only partially prevented the inhibition induced by APGWamide and GWamide on F2 neurons. Combination of TEA (5 mM) and 4-AP (250 microM) could abolish this inhibition. However, neither 1 mM La2+ nor 10 mM Co2+ could prevent the inhibitory action of APGWamide and GWamide. This evidence indicates that the postsynaptic inhibition of APGWamide and GWamide on F2 neurons is due to an increase in K+ conductance and that both transient K channel (IA) and delay K+ channel (IK) were affected by these peptides. 4. APGWamide and GWamide exert both presynaptic and postsynaptic effects of Helix neurons, depending on the neuron under study. They are qualitatively and quantitatively similar in their presynaptic or postsynaptic actions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

An initial screen of a series of neuroactive peptides for activity on identified central neurones of Helix aspersa.

1. Intracellular recordings were made from identified neurones in the suboesophageal ganglia of Helix aspersa. Seven neuropeptides were tested for activity and their actions compared with acetylcholine and FMRFamide. 2. Three peptides isolated from nematodes, AF-1, AF-2 and PAN-1 had mainly inhibitory effects with thresholds of around 1 nM. This inhibition was due to an increase in potassium conductance. 3. The molluscan neuropeptides LSSFVRIamide, CARP and ACEP-1 were all active on certain neurones; the first two showed only inhibitory effects while ACEP-1 was mainly excitatory. The thresholds in each case were 0.1-10 microM. When norleucine replaced methionine in CARP, the potency was reduced by at least 100 times. 4. The echinoderm peptide, SALMF-1, only excited neurones but with a very low threshold, around 1.0 fM. 5. There was no obvious correlation between the action of these peptides and either acetylcholine or FMRFamide.

Acetylcholine↗
PubMed1992

The action of a series of glutamic acid analogues on Helix neuronal glutamate receptors.

1. Intracellular recordings were made from identified Helix central neurones, sensitive to L-glutamate. 2. Out of a range of substituted glutamate analogues, only the L- and D-isomers of thio-glutamate possessed clear glutamate-like activity. 3. On neurones excited by L-glutamate, the EC50 values for L-glutamate, gamma-thio-L-glutamate and gamma-thio-D-glutamate were 30 microM, 20 microM and greater than 1 mM, respectively. 4. On neurones inhibited by L-glutamate, the EC50 values for L-glutamate, gamma-thio-L-glutamate and gamma-thio-D-glutamate were 6.0 microM, 0.7 microM and greater than 200 microM, respectively. 5. It is concluded that, unlike the situation with thio derivatives of GABA, thio derivatives of glutamate possess potent glutamate-like activity.

Animals↗