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Biomedical subjects

R J Walker

Publications and source records attributed to R J Walker.

At least 217 records · Page 12Linked to original sources
PubMed1984

Neuropharmacological studies on the receptors mediating responses to carbachol, amino acids and octopamine on Limulus and Hirudo central neurons.

Intracellular recordings were made from central neurons of Limulus polyphemus and from Retizu cells of the leech, Hirudo medicinalis. The effects of carbachol, amino acids and octopamine were examined on these neurons. Octopamine was found to have a mainly inhibitory effect on a few Limulus neurons. The effects of octopamine were mimicked by clonidine and napthazoline but not by xylazine. Both compounds were slightly more potent than octopamine. Yohimbine, metoclopramide, chlorpromazine and chlordimeform failed to antagonize this octopamine response. The excitatory effect of carbachol was blocked by alpha-bungarotoxin, 10(-7)M. Neither this concentration nor higher concentrations of alpha-bungarotoxin had any effect on L-glutamate excitation. m-Carboxyphenyl derivatives of alanine and glycine acted differentially on Limulus neurons responding to L-glutamate. m- Carboxyphenylglycine only inhibited neurones which showed a biphasic response to L-glutamate while m- carboxyphenylalanine only excited these neurons. Both compounds excited leech Retzius cells, with m- carboxyphenylalanine being about 20 times more potent than m- carboxyphenylglycine . The actions of alpha- ketokainate and allo-alpha- ketokainate were compared to kainate, dihydrokainate and L-glutamate on leech Retzius cells. The equipotent molar ratios for kainate, dihydrokainate , alpha- ketokainate and allo-alpha- ketokainate were 0.0029 +/- 0.0004, 0.021 +/- 0.047, 0.029 +/- 0.005 and 0.14 +/- 0.0093 respectively with L-glutamate as one. All the analogues were more potent than L-glutamate. Quinolinic acid had no glutamate-like activity on either Limulus or Hirudo neurons. Methyltetrahydrofolate was inactive on Limulus neurons but excited leech Retzius cells, being slightly less potent than L-glutamate. Dibutyl cAMP terminated the excitatory actions of kainate on both Limulus and Hirudo neurons. Anisatin , a putative GABA antagonist, was a potent antagonist of GABA inhibition on Limulus neurons.

Amino Acids↗
PubMed1984

The halomethylketone derivative L-Glu-gamma-DL-Ala-CH2Cl and N-methyl-D-aspartate as selective antagonists against L-glutamate and kainate excitation respectively on Retzius cells of the leech, Hirudo medicinalis.

Intracellular recordings were made from leech Retzius cells. The action of a range of putative antagonists was examined on the excitatory responses to dicarboxylic amino acids which were applied via a diffusion electrode. The halomethylketone derivative, L-Glu-gamma-DL-Ala-CH2Cl was found to block preferentially the L-glutamate response compared to the kainate response. This compound had no effect on the response to carbachol. N-Methyl-D-aspartate was found to block the response to kainate while having no effect on the responses to L-glutamate, ibotenate or carbachol. This compound had no direct action on the cell. N-Methyl-D-aspartic acid also reduced the excitatory responses to methyltetrahydrofolate and 3- carboxymethylpyrrolidine -2,4-dicarboxylic acid ( CMPDA ). gamma-D-Glutamyl-amino methyl-sulphonate ( GAMS ), while partially blocking the action of kainate, had no effect on the response to ibotenate. gamma-D-Glutamylglycine was found to reduce the response to L-glutamate, ibotenate, kainate, quisqualate and CMPDA . CMPDA , a tricarboxylic acid derivative of kainate, was found to be approximately equipotent with kainate on leech Retzius cells. This compound was partially blocked by N-methyl-D-aspartate. The present study demonstrates that it is possible to differentially block L-glutamate and kainate on leech Retzius cells and indicates that they are acting on separate components of the membrane.

Amino Acid Chloromethyl Ketones↗
PubMed1984

The possible site of action of 5-hydroxytryptamine, 6-hydroxytryptamine, tryptamine and dopamine on identified neurons in the central nervous system of the snail, Helix aspersa.

Intracellular recordings were made from identified neurons in the right parietal ganglion of the snail, Helix aspersa. Cells F 4, 5 and 6 were excited by 5-hydroxytryptamine (5-HT) and inhibited by dopamine while cells in the F 30 area were inhibited by both compounds. Low doses of both tryptamine and 6-HT produced weak excitation of cells F 4, 5 and 6 while higher doses of both compounds inhibit the activity of these cells. In terms of the inhibitory responses, tryptamine and 6-HT are approximately equipotent but between 10 and 100 times less potent than dopamine. d-Tubocurarine reversibly antagonized the excitatory action of 5-HT on cells F 4, 5 and 6 and converted tryptamine and 6-HT excitation to inhibition. In the presence of the antagonist, ergometrine, the dopamine inhibitory response was almost completely abolished while the inhibitory responses to tryptamine and 6-HT were converted to weak excitation. All four agonists inhibited cells in the F 30 area with the following potency ratios: dopamine much greater than tryptamine/6-HT greater than 5-HT. Tubocurarine had no antagonist effects on these responses while ergometrine reduced or blocked all four, often irreversibly. In potassium-free Ringer the inhibitory responses to all four agonists were enhanced. It is concluded that on cells F 4, 5 and 6, low concentrations of tryptamine and 6-HT act on 5-HT receptors while higher concentrations of both agonists act on dopamine receptors. On cells in the F 30 area, 5-HT, 6-HT and tryptamine all act on a dopamine receptor.

Animals↗
PubMed1984

The ionic mechanisms associated with the excitatory response of kainate, L-glutamate, quisqualate, ibotenate, AMPA and methyltetrahydrofolate on leech Retzius cells.

Intracellular recordings were made from Retzius cells from segmental ganglia of the leech, Hirudo medicinalis. The ionic mechanisms of the following compounds were examined: L-glutamate, ibotenate, quisqualate, AMPA, kainate, methyltetrahydrofolate and carbachol. All these compounds depolarise and excite Retzius cells. In sodium-free Ringer, the responses to L-glutamate, kainate, ibotenate and AMPA were greatly reduced, the response to quisqualate was reduced, the response to methyltetrahydrofolate was normal while the response to carbachol was abolished. In sodium-free high calcium Ringer the responses to L-glutamate, ibotenate and carbachol were absent, the responses to quisqualate and AMPA greatly reduced, the responses to methyltetrahydrofolate and kainate were normal. The methyltetrahydrofolate and kainate responses in sodium-free high calcium Ringer were greatly reduced on addition of cobalt. All the responses are associated with an increase in conductance, the increase being the largest in the case of kainate. It is concluded that the response to L-glutamate, ibotenate and carbachol are dependent on sodium, the responses to quisqualate and AMPA are mainly sodium dependent, possibly with a small calcium component. The kainate response in normal Ringer is largely sodium dependent but in sodium-free Ringer calcium can completely substitute for sodium. The methyltetrahydrofolate response appears to be sodium independent but at least partly calcium dependent. These studies provide further evidence that L-glutamate and ibotenate act on a common receptor on leech Retzius cells while kainate acts on a separate receptor which can activate a calcium ionophore. It is probable that methyltetrahydrofolate acts on a different ionophore system to kainate. N-Methyl-D-aspartate has no agonist activity on any of these receptors.

Action Potentials↗
PubMed1984

D-penicillamine-induced myasthenia gravis in primary biliary cirrhosis.

A 62-yr-old woman with recently diagnosed primary biliary cirrhosis was started on D-penicillamine, 250 mg twice daily. Within 9 mo, she developed myasthenia gravis, associated with elevated antiacetylcholine receptor antibody titers and abnormalities of single-fiber electromyography. The D-penicillamine was withdrawn and pyridostigmine bromide was prescribed. The latter drug was slowly reduced, and at the end of 6 mo stopped, after a full recovery by the patient. The clinical response was paralleled by a fall in the antiacetylcholine receptor antibody titer into the normal range and reversal of the previously abnormal single-fiber electromyographic findings. The human leukocyte antigen type of the patient was not that typically associated with classic myasthenia gravis. It is suggested that D-penicillamine-induced myasthenia gravis is due to an independent effect of the drug on the immune system rather than to the unmasking of subclinical myasthenia gravis.

Autoantibodies↗
PubMed1983

Injection sclerotherapy for oesophageal varices in the elderly.

Thirty-seven patients admitted consecutively to the Gastroenterology Unit with haemorrhage from oesophageal varices were treated by injection sclerotherapy. The patients were subdivided according to age at presentation (below 65, over 65 years). The mortality and morbidity of the two groups, over the period of follow-up (mean 5.1 months) were compared. The risk of rebleeding was higher in the elderly (0.23 overall) than in the young (0.11 overall) and was reflected in the higher mortality, four of 14 elderly patients and four of 23 younger patients. A further three elderly patients succumbed to intercurrent illness during the same period. In three of the surviving elderly, complete resolution of varices was noted. Complications of sclerotherapy occurred in eight out of 51 injections in the elderly and six out of 97 in the young but were usually well tolerated. This study suggests that injection sclerotherapy is useful in the treatment of bleeding oesophageal varices in the elderly and suggests recommendations for improved survival.

Adult↗
PubMed1983

Interactions between alinidine and responses to acetylcholine, dopamine and 5-hydroxytryptamine of specific Helix central neurones.

Intracellular recordings were made from identified neurones in the brain of the snail, Helix aspersa. The effect of alinidine on the excitatory and inhibitory responses to acetylcholine and dopamine and on the excitatory response to 5-hydroxytryptamine (5-HT) was investigated. Alinidine was found to reduce the responses to acetylcholine and 5-HT and the excitatory response to dopamine but had no effect on the dopamine inhibitory response. pA2 values were determined for alinidine antagonism to indicate relative potency. The pA2 values against the excitatory responses of acetylcholine, dopamine and 5-HT were 5.8, 5.6 and 5.5 respectively. The pA2 value against acetylcholine inhibition was 3.5. From these studies it is suggested that alinidine interacts preferentially with the sodium inonophore, to a lesser degree with the chloride ionophore and not at all with the potassium ionophore on Helix central neurones.

Acetylcholine↗
PubMed1982

Are HLA antigens important in the development of alcohol-induced liver disease?

The prevalences of 10 HLA-A and 16 HLA-B antigens were determined in 50 patients with alcoholic cirrhosis and 120 alcoholic patients without cirrhosis and compared with those in a control group of 550 healthy subjects from the same geographical area. B40 was absent in the patients with cirrhosis but was found in 18 (15%) of the patients without cirrhosis (p = 0.0087). No other association was noted. It is concluded that there is no good evidence to date of an association between HLA antigen state and susceptibility to alcohol-induced cirrhosis.

ABO Blood-Group System↗
PubMed1982

gamma-D-glutamylglycine as an antagonist of kainic acid on leech Retzius neurones.

Intracellular recordings were made from Retzius cells from the segmental ganglia of the leech, Hirudo medicinalis, gamma-D-Glutamylglycine, (50 microM), reversibly and preferentially antagonised the excitatory action of kainate, having no effect on actions of quisqualate or carbachol but at this concentration the antagonism was of short duration, reversing prior to washing off the gamma-D-glutamylglycine. However, higher concentrations of gamma-D-glutamylglycine (250-500 microM) reversibly antagonised both quisqualate and carbachol-induced excitatory responses, indicating a lack of specificity. The value of gamma-D-glutamylglycine in determining the possible site of action of kainate on leech Retzius cells is discussed.

Animals↗
PubMed1982

The activity of cis and trans -2- (aminomethyl) cyclopropane carboxylic acids on GABA - related mechanisms in the central nervous system of Limulus and Periplanata and of mammals.

Some pharmacological actions of (+/-) - cis - and (+/-) - trans -2-(aminomethyl) cyclopropane carboxylic acids, conformationally restricted analogues of GABA, are described. The trans isomer (TAMP) was 17 and 4.5 times less active than GABA in hyperpolarising central neurones of Limulus and Periplanata and 10.8 times less active in displacing [3H]-muscimol from rat brain membranes. The cis isomer (CAMP) was ineffective on Limulus neurones at 35 mumoles, 650 times less active on Periplanata neurones and only weakly displaced [3H]-muscimol at 100 microM. Neither isomer inhibited synaptosomal uptake of [3H]-GABA at 100 microM. These data suggest that the invertebrate receptors studied respond to GABA in an extended conformation.

Animals↗
PubMed1982

The pharmacology of Limulus central neurons.

1. Intracellular recordings have been made from neurons in the central nervous system of the horse-shoe crab, Limulus polyphemus. Neurons possess resting potentials between -40 and -60 mV, with action potentials ranging from 2-3 mV up to 60 mV in amplitude. Neurons also have excitatory and inhibitory postsynaptic potentials. 2. All the neurons studied are inhibited by GABA and excited by cholinomimetics. The GABA response is chloride mediated and reversibly antagonised by picrotoxinin but not by bicuculline or bicuculline methochloride or methoiodide. The cholinergic response is nicotinic and blocked by pentolinium, hexamethonium, chlorisondamine and dihydro-beta-erythroidine. 3. L-Glutamate can excite some cells, inhibit others and have a biphasic action, inhibition followed by excitation, on other cells. The inhibitory effect is chloride mediated and blocked by picrotoxinin. Ibotenate mimics the action of glutamate both in terms of inhibition and excitation but kainate and quisqualate only mimic the excitatory action of L-glutamate. 4. Dopamine, octopamine, 5-hydroxytryptamine and histamine excite some neurons while inhibiting others or have a biphasic action. Dopamine and octopamine normally have different effects on the same cell, suggesting they act via different receptors. Octopamine shows stereospecificity for the (-) isomer which is more than 100 times more active than the (+) isomer and octopamine is reversibly antagonised by phentolamine and cyproheptadine. 5. Proctolin has an excitatory action on these neurons and this effect is long lasting and can be potentiated by dibutyl cyclic AMP. 6. The pharmacology of Limulus central neurons is compared to the pharmacology of insect and crustacean central neurons. It is concluded that GABA and acetylcholine are central transmitters throughout the arthropods. It is also probable that L-glutamate and octopamine have a physiological role in the arthropod central nervous system. Proctolin appears to modify neuronal and muscle activity in the arthropods and has a modulatory or transmitter function.

Acetylcholine↗
PubMed1982

The excitatory actions of a series of piperidine dicarboxylates on central neurons of the rat, snail, leech and horseshoe crab and on crab neuromuscular junction.

1. Intracellular recordings were made from Helix, Hirudo and Limulus central neurons and from Eupagurus leg muscle and extracellular recordings from rat lateral geniculate neurons. The actions of 2,3-, 2,4-, 2,5- and 2,6-piperidine dicarboxylates were tested on those preparations for both direct effects and interactions with the response to L-glutamate. 2. All four piperidine analogues were devoid of either reproducible direct or indirect effects on Helix and Limulus neurons save that the 2,5-analogue did mimic the action of L-glutamate on Limulus neurons which were inhibited by glutamate. 3. On Hirudo and rat neurons and on Eupagurus muscle, all four piperidines mimicked the action of L-glutamate, all were weak agonists on rat neurones while on Hirudo neurons the 2,5-analogue was the most potent but on Eupagurus muscle, the 2,3- and 2,6-analogues were the most potent. 4. All four piperidines potentiated the action of L-glutamate on rat and Hirudo neurons and on Eupagurus leg muscle and of muscle ejps. 5. The piperidine analogues indicate that there are differences between the glutamate receptors used in the present study and provide some supportive evidence that the preferred conformation for glutamate on crab leg muscle is partially folded while for Hirudo neurons it is more extended.

Animals↗