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J T Williams

Publications and source records attributed to J T Williams.

At least 145 records · Page 8Linked to original sources
PubMed1987

Naloxone-induced depolarization and synaptic activation of myenteric neurons in morphine-dependent guinea pig ileum.

To investigate the cellular basis of opiate dependence, intracellular microelectrodes were used to record from both electrophysiologically defined classes of neurons (S and AH) in myenteric plexus longitudinal muscle preparations from morphine pretreated guinea pigs. These preparations responded to naloxone with the characteristic contraction of the longitudinal smooth muscle, indicative of morphine dependence. Depolarization in response to naloxone was observed in 42% of S neurons, but there were no consistent changes in input resistance. In some cells the depolarization was reduced or abolished after blockade of synaptic transmission, suggesting that it was due in part to the release of an excitatory transmitter producing a slow depolarization in the impaled neuron. Synaptic activation of S neurons during withdrawal was further indicated by the observation that fast postsynaptic potentials appeared after abrupt displacement of morphine from its receptors by naloxone. Morphine withdrawal, therefore, involves both the final motor neurons and interneurons. During naloxone-induced withdrawal, 25% of S neurons discharged action potentials. In contrast, no action potentials were discharged in AH neurons. Furthermore, naloxone did not alter the resting membrane potential, input resistance, soma action potential configuration, or slow hyperpolarization following a soma spike in AH neurons. The specificity of the withdrawal response for S neurons and the relatively small proportion of neurons involved suggests that morphine withdrawal occurs in quite specific neuronal circuits in the myenteric plexus.

Animals↗
PubMed1987

Mu and delta receptors belong to a family of receptors that are coupled to potassium channels.

The effects of agonists at mu and delta opioid receptors were compared by measuring membrane currents under voltage clamp from neurons of the rat nucleus locus coeruleus and guinea pig submucous plexus. In each tissue, the appropriate selective agonist (Tyr-D-Ala-Gly-MePhe-Gly-ol for mu receptors in locus coeruleus or Tyr-D-Pen-Gly-Phe-D-Pen for delta receptors in submucous plexus) increased the conductance of an inwardly rectifying potassium conductance and strongly hyperpolarized the membrane. The properties of the potassium conductance affected by the two opioids could not be distinguished. Experiments with intracellular application of guanosine 5'-[gamma-thio]triphosphate indicated that a guanine nucleotide-binding regulatory protein was involved in the coupling between opioid receptor and potassium channel, but there was no evidence for activation of either cAMP-dependent protein kinase or protein kinase C. It is noted that a number of vertebrate neurotransmitter receptors are coupled to potassium channels. The potassium conductance associated with these channels has properties similar to the conductance activated by mu and delta opioids; this family includes the following receptors: acetylcholine M2, norepinephrine alpha 2, dopamine D2, 5-hydroxytryptamine 5-HT1, adenosine A1, gamma-aminobutyric acid GABAB, and somatostatin. It is suggested that this conductance is a conserved neuronal effector coupled to one of the receptor types that mediates the effects of each of several major transmitters. The mu and delta opioid receptors appear to be unusual in that both utilize this same effector mechanism.

Animals↗
PubMed1987

Inhibitory synaptic potentials recorded from mammalian neurones prolonged by blockade of noradrenaline uptake.

1. Intracellular recordings of membrane potential and membrane current were made from neurones of the rat nucleus locus coeruleus and the guinea-pig submucous plexus. These neurones exhibit inhibitory post-synaptic potentials (i.p.s.p.s) which result from noradrenaline acting on alpha 2-adrenoceptors to cause an increase in potassium conductance. 2. Cocaine (0.2-30 microM) reversibly increased the duration of the i.p.s.p. or inhibitory post-synaptic current (i.p.s.c.) in locus coeruleus neurones and submucous plexus neurones by approximately 750% and 350% respectively. The concentrations of cocaine causing half-maximal prolongation of the synaptic current were 3 microM in locus coeruleus and 0.5 microM in submucous plexus. The prolongation was due entirely to a slower rate of decay of the synaptic response. 3. Cocaine (10 microM) produced a maintained hyperpolarization (2-10 mV) or outward current (20-120 pA) in locus coeruleus neurones; in submucous plexus neurones cocaine increased the amplitude and duration of spontaneous i.p.s.p.s. 4. Outward currents produced by superfusion with noradrenaline were increased by cocaine with maximum effects being observed at 10-30 microM-cocaine. The maximum leftward shift in the relation between outward current or membrane hyperpolarization and noradrenaline concentration was 18- to 100-fold in locus coeruleus neurones and 4-fold in submucous plexus neurones. The concentrations of cocaine which caused a half-maximal increase in sensitivity to superfused noradrenaline were similar in both tissues, being 4 microM in locus coeruleus and 2 microM in submucous plexus. 5. These results show that neuronal uptake of noradrenaline released from adrenergic nerves plays a significant role in determining the time course of synaptic potentials mediated by noradrenaline.

Action Potentials↗
PubMed1987

Cellular mechanisms of opioid tolerance: studies in single brain neurons.

Intracellular recordings of membrane potassium current were made from rat locus coeruleus in vitro. The effects of agonists at mu-opioid receptors were studied on neurons from rats that had been chronically treated with morphine; these were compared with actions on neurons from control rats. Tolerance to the opioid-induced increase in potassium conductance was observed, and this was more pronounced for normorphine than for [Met5]enkephalin and [D-Ala2, Mephe4, Gly5-ol]enkephalin: experiments with the irreversible receptor blocker beta-chlornaltrexamine indicated that normorphine had lower intrinsic efficacy than [Met5]enkephalin and [D-Ala2 MePhe4, Gly5-ol]enkephalin. This adaptation was not due to any change of the properties of the potassium conductance activated by mu-receptors because both full and partial agonists at alpha 2-adrenoceptors, which couple to the same potassium conductance, were unchanged in their effectiveness; nor was it associated with any change in the affinity of mu-receptors for the antagonist naloxone. Naloxone had no effect on the neurons other than simple competitive reversal of the action of the mu-receptor agonists. These results demonstrate that 1) the mechanism responsible for tolerance in locus coeruleus neurons is specifically associated with mu-receptors and/or their coupling to potassium channels, 2) the intrinsic efficacy of an opioid determines the degree of tolerance observed, and 3) tolerance and physical dependence can be dissociated at the cellular level.

Animals↗
PubMed1987

Membrane properties and adrenergic responses in locus coeruleus neurons of young rats.

Intracellular recordings were made from locus coeruleus neurons in slices taken from rats 8-26 d of age. Neurons from these animals exhibited spontaneous action potentials, which were superimposed on slow (0.3-3 Hz) rhythmic depolarizations. The frequency of these potentials was closely related to the age of the animals from which the slice was taken, the slowest frequencies being observed in tissues from the youngest animals. In adult animals, such rhythmic activity was only rarely observed under normal recording conditions. The rhythmic depolarizations had a slow rate of rise and fall, were 3-15 mV in amplitude, were not affected by tetrodotoxin, and were abolished in solutions that contained elevated magnesium content. When the membrane potential was hyperpolarized by passing current through the recording electrode, the depolarizing rhythmic activity persisted even at very negative potentials (-120 mV). These depolarizations appear to be generated by the inward movement of calcium ions, probably in dendritic regions of the neuron. Superfusion of phenylephrine caused membrane depolarizations, increased the frequency of action potentials and of the slow, rhythmic depolarizations in about 80% of the cells from young rats, whereas it had no effect or a depressant action on cells from adults. Noradrenaline hyperpolarized the cells through an alpha 2-adrenoceptor and abolished the slow depolarizations. In cells from young rats, the hyperpolarization produced by noradrenaline reached a maximum and then declined, such that there was a "sag" in the membrane potential toward the resting potential following the peak of the hyperpolarization. Following the washout of noradrenaline, the membrane potential repolarized before moving toward the resting level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1987

Potentiation of enkephalin action by peptidase inhibitors in rat locus ceruleus in vitro.

Intracellular recordings were made from locus ceruleus (LC) neurons in slices of rat pons. It has been shown previously that opioids inhibit firing and hyperpolarize LC neurons by activating mu-opioid receptors. Concentration-response curves were constructed by measuring the hyperpolarization, or outward current at -60 mV, caused by various opioid agonists added to the superfusing solution. Peptidase inhibitors (kelatorphan, bestatin and thiorphan) each increased the potency of Met-enkephalin, Leu-enkephalin and metorphamide but had no effect of their own on the LC neurons. Kelatorphan (20 microM) produced a 7-fold shift to the left of the Met-enkephalin dose-response curve. Higher concentrations produced no further shift. Thiorphan (3 microM) and bestatin (20 microM) each had a smaller potentiating effect on the Met-enkephalin hyperpolarization. The effects of Tyr-D-Ala-Gly-MePhe-Gly-ol and noradrenaline were not potentiated by these peptidase inhibitors. Electrical stimulation produced an inhibitory synaptic potential that was prolonged by cocaine (10 microM) and blocked by the alpha-2 adrenoceptor antagonist idazoxan (1 microM). After addition of idazoxan, hyperpolarizing synaptic potentials could be evoked even in the presence of kelatorphan (20 microM). These results indicate that peptide metabolism in the intact brain slice can account for a substantial decrease in the sensitivity of LC neurons to exogenously applied opioid peptides; even after peptidase inhibition, no evidence could be obtained for hyperpolarizing synaptic potentials due to the release of endogenous opioids.

Analgesics↗
PubMed1987

Bronchoalveolar lavage of the live anaesthetised sheep.

Segmental lavage was performed on anaesthetised adult sheep using either endoscopic catheterisation or fibreoptic bronchoscopy. Cellular and humoral data were compared with results obtained from gross lavage of whole excised lungs. Both techniques proved rapid, convenient and reproducible, providing sufficient material for qualitative and quantitative assays of respiratory cells and fluid. Although total cells per unit volume of fluid obtained by catheterisation or by bronchoscopy were decreased compared with whole lung lavage, differential cell populations, fluid recovery and immunoglobulin and complement (C3) concentrations were comparable.

Anesthesia, General↗
PubMed1986

Membrane potential measured during potassium-evoked release of noradrenaline from rat brain neurons: effects of normorphine.

A single slice of rat pons that contained the locus ceruleus (LC) or two slices of cerebellum were loaded with [3H]noradrenaline; superfusion with high (35 or 60 mM) potassium solutions evoked a release of 3H. In the presence of normorphine, the release of 3H evoked by 35 mM potassium and 60 mM potassium was reduced. In some of those experiments in which the release of 3H from the LC slice was measured, an intracellular microelectrode was used to measure membrane potential. This showed that solutions of increased potassium concentration depolarized the neurons to a potential at which inward calcium currents flowed (calcium action potentials occurred). Normorphine hyperpolarized the neurons; during this hyperpolarization the depolarization caused by 35 mM potassium did not reach the threshold for significant calcium entry. The results suggest that the inhibition by normorphine of transmitter release evoked by solutions of raised potassium concentration could result in part from the membrane hyperpolarization caused by the normorphine.

Action Potentials↗
PubMed1986

Tolerance to opioids in single locus coeruleus neurons of the rat.

Chronic treatment of rats with morphine caused tolerance to the membrane hyperpolarizing action of morphine in single locus coeruleus neurons in vitro. Tolerance was less pronounced for Try-D-Ala-Gly-MePhe-Gly-ol (DAGO) than for normorphine. No changes were found in affinity of naloxone for mu-receptors on these neurons, nor in the properties of the potassium conductance increase caused by mu-receptor activation. These results suggest that the mechanisms underlying tolerance involve either a reduction of the number of mu-receptors on each cell, or a reduced coupling of mu-receptors to potassium channels.

Animals↗
PubMed1985

Quantitative assessment of tooth wear, alveolar-crest height and continuing eruption in a Romano-British population.

Although measurements from cement-enamel junction (CEJ) to alveolar crest (AC) have been used in assessing changes in alveolar-crest height as age or chronic inflammatory periodontal disease (CIPD) progresses, there is evidence from ancient populations that the position of AC remains almost constant throughout life and continuing eruption to compensate for attrition may explain why CEJ-AC measurements increase with age. Measurements of occlusal attrition and relationship of CEJ to AC were made on the cheek teeth of 500 Romano-British skulls by direct measurement or by reference to the fixed line of the inferior alveolar canal (IAC) on radiographs. Direct measurements indicated that there were usually no statistical differences between the vertical amounts of tooth substance lost by attrition and the change in the distance CEJ-AC as age progressed. Measurements on radiographs showed that posterior teeth continued to erupt to compensate for attrition and the AC remained static as age progressed. Bone deposition at the AC was seen in the majority of ground sections. Thus tooth wear appears to be compensated by continuing movement of teeth in an occlusal direction. The position of the AC remained almost constant throughout life; AC bone lost by CIPD seemed to be replaced during continuing tooth eruption.

Age Factors↗
PubMed1985

Characterization of alpha 2-adrenoceptors which increase potassium conductance in rat locus coeruleus neurones.

Intracellular recordings were made from locus coeruleus neurones in a slice of rat pons superfused in vitro. A single-electrode voltage-clamp amplifier was used to measure membrane currents. Superfusion of the slice with clonidine (3-100 nM) or noradrenaline (100 nM-100 microM), or brief application of noradrenaline from a pipette by a pressure pulse, caused dose-dependent membrane hyperpolarizations. Phenylephrine (10 microM) and isoprenaline (10 microM) were ineffective. The hyperpolarizations were accompanied by a decrease in neurone input resistance. The hyperpolarization evoked by pressure ejection of noradrenaline could be reversed by membrane polarization to -110 mV. Clonidine and noradrenaline caused a membrane current which was linearly related to membrane potential between -50 and -120 mV, being outward at resting levels and reversing at -110 mV. The concentration-response curves for clonidine and noradrenaline were shifted rightwards in a parallel manner by alpha 2-adrenoceptor antagonists. The antagonist KeS estimated from the degree of shift were: RX 781094 9 nM, yohimbine 14 nM, phentolamine 20 nM and piperoxane 49 nM. These experiments indicate that in locus coeruleus neurones an increase in potassium conductance results from activation of alpha 2-adrenoceptors similar to those characterized on peripheral neurones.

Animals↗
PubMed1985

Catecholamine inhibition of calcium action potentials in rat locus coeruleus neurones.

Intracellular recordings were made from neurones in the nucleus locus coeruleus in a slice of tissue cut from the rat pons. Clonidine (100 nM-10 microM), noradrenaline (10 microM-1 mM) and adrenaline (10 microM-1 mM) all reduced the duration of the spontaneously occurring action potential of the neurones. This effect was also observed on the action potential in the presence of tetrodotoxin, which results from calcium entering the cell. These concentrations of clonidine, noradrenaline and adrenaline always hyperpolarized the membrane. This hyperpolarization was prevented by two procedures which block potassium currents--intracellular caesium and extracellular barium. In conditions of potassium current blockade, noradrenaline (100 microM-1 mM) and adrenaline (20 microM-1 mM) shortened the calcium action potential but clonidine was ineffective even at 10 microM. Adrenaline and noradrenaline also suppressed inward calcium and barium currents measured under voltage clamp. This action of noradrenaline and adrenaline was not prevented by yohimbine (10 microM), propranolol (20 microM) or prazosin (1 microM); it was reduced by a concentration of phentolamine about 100 times higher than its Ke for alpha 2-adrenoceptors on locus coeruleus neurones. It is concluded that noradrenaline and adrenaline can directly inhibit calcium action potentials in locus coeruleus neurones when applied in high concentrations, but that this does not involve an alpha 2-adrenoceptor.

Action Potentials↗
PubMed1985

On the potassium conductance increased by opioids in rat locus coeruleus neurones.

Intracellular recordings were made from locus coeruleus neurones in slices cut from rat pons and superfused in vitro. Membrane currents were recorded with a single-electrode switch-clamp amplifier. Opioids, enkephalin analogues or morphine, caused a concentration-dependent potassium current, which had a maximum value of about 300 pA at -60 mV. The opioid-sensitive potassium conductance was independent of membrane potential between -60 and -130 mV, but became less as the membrane potential was changed from -60 to -30 mV. The opioid outward current was reduced by quinine (100 microM-1 mM) and barium (30 microM-2 mM), but not by 4-aminopyridine (100 microM-1 mM) or tetraethylammonium (10 mM). A potassium current with similar properties flowed for several seconds after a burst of action potentials; this appeared to result from calcium entering the neurone during the action potentials. The alpha 2-adrenoceptor agonists noradrenaline and clonidine caused a concentration-dependent potassium conductance increase which had the same maximum value as that caused by opioids in the same neurones. Experiments in which an opioid and an alpha 2-adrenoceptor agonist were superfused together indicated that the same potassium conductance is increased by both agonists.

Action Potentials↗
PubMed1985

Subphrenic abscess: a complication of lobar pneumonia.

A patient presented with a pneumococcal lobar pneumonia and later developed a subphrenic abscess. Peritonitis and intra-abdominal abscess formation should be remembered as a rare cause of delayed recovery from lobar pneumonia.

Blood Transfusion↗
PubMed1984

Use of pyrethroid impregnated tags in the control of sheep headfly disease.

Plastic tags containing 8.5 per cent w/w cypermethrin or 10 per cent w/w permethrin reduced the severity of damage caused to sheep by the headfly Hydrotaea irritans. A similar pattern of protection extended from the tagged ewes to their untagged lambs. Tags containing 8.5 per cent w/w fenvalerate failed to reduce the level of headfly damage in gimmers.

Animals↗
PubMed1984

Evaluation of three synthetic pyrethroids in the control of sheep headfly disease.

Deltamethrin (0.01 per cent) applied to the heads of lambs and gimmers at 30 day intervals on two separate farms failed to control damage caused by the sheep headfly , Hydrotaea irritans. Permethrin (0.1 per cent) applied to gimmers at monthly intervals achieved a slight reduction in severity of damage but protection did not extend beyond 14 days. Polyvinyl chloride tags containing 8.5 per cent cypermethrin reduced damage in gimmers to a very low level with protection lasting throughout the summer. Weight gains of lambs suffering headfly damage were significantly less than unaffected lambs.

Animals↗