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G Henderson

Publications and source records attributed to G Henderson.

At least 91 records · Page 5Linked to original sources
PubMed1990

The sigma [corrected] ligand rimcazole antagonises (+)SKF 10,047, but not (+)3-PPP, in the mouse isolated vas deferens.

We have characterized the actions of several sigma receptor ligands on the electrically evoked, neurogenic contractions of the mouse isolated vas deferens. (-)SKF 10,047 was significantly more potent than (+)SKF 10,047 in potentiating twitch contractions and was equipotent with (+)3-PPP. Rimcazole (1 and 3 microM) antagonised the potentiation induced by 100 microM (+)SKF 10,047 and, to a lesser extent, that induced by 30 microM (-)SKF 10,047 but increased that elicited by (+)3-PPP (30 microM). This apparent contradiction may arise from sigma agonists acting in this tissue at both sigma and non-sigma sites.

Animals↗
PubMed1990

Characterization of two components of the N-like, high-threshold-activated calcium channel current in differentiated SH-SY5Y cells.

Retinoic acid differentiated SH-SY5Y cells exhibit only a high-threshold-activated (-30 to -20 mV) whole cell calcium channel current. When barium was used as the charge carrier, the high-threshold-activated current showed bi-exponential inactivation kinetics during a 500 ms voltage step from -90 to +10 mV. The time constants of inactivation were approximately 75 and 750 ms. The fast inactivating component was more sensitive than the slow inactivating component to steady-state inactivation at depolarized holding potentials. The calcium channel current was inhibited by externally applied cadmium (10-300 microM) and gadolinium (10-30 microM) as well as by high concentrations of nickel and cobalt. omega Conus toxin (1 microM) irreversibly blocked the calcium channel current. However, the dihydropyridine agonist, BAY K 8644 (3-10 microM) and antagonists, nifedipine (3-10 microM) and nimodipine (10 microM) did not affect either component of the calcium channel current. Agents which blocked the calcium channel current did not exhibit any selectivity for the fast inactivating over the slow inactivating component of the current. These results indicate that whilst the calcium channel current recorded in differentiated SH-SY5Y cells can be classified on the basis of the blocking agents as being of the N type, the current shows more than one form of inactivation.

Calcium Channel Agonists↗
PubMed1990

Characterization of the neurons of the mouse hypogastric ganglion: morphology and electrophysiology.

The somata of mouse hypogastric ganglion cells injected with Lucifer yellow were ovoid in shape, lacked dendritic processes but gave rise to a single axonal process. Antidromic activation demonstrated that some of the cells contained in this ganglion innervated the vas deferens. The passive and active membrane properties of the ganglion cells were determined in current clamp experiments. Cells fired tetrodotoxin-sensitive action potentials in response to intracellularly-applied depolarizing current. In voltage clamp evidence was obtained for both a persistent inward calcium current at potentials between -30 and -40 mV and a transient calcium current evoked by step depolarizations to around -20 mV. In current clamp, however, cells did not fire calcium action potentials in the presence of tetrodotoxin. Three potassium currents, IM (blocked by 1 mM barium and by 30 microM bethanechol), IA (blocked by 2 mM 4-aminopyridine) and IK(Ca) fast (blocked by 100 microM cadmium and by 5 mM tetraethylammonium) were characterized in these neurons. In addition, IK(Ca) slow was observed in a small proportion of cells. Fast, all-or-nothing, excitatory synaptic potentials were recorded in response to single stimuli applied to the afferent fibres running to the ganglion. In most cells the excitatory synaptic potentials were suprathreshold for action potential initiation and were markedly reduced or abolished by 100 microM mecamylamine, 1 mM hexamethonium and following desensitization to 100 microM nicotine. Excitatory synaptic potentials arose from stimulation of a single presynaptic nerve process and are typical of strong synaptic inputs.

Action Potentials↗
PubMed1990

Inhibition of potassium currents by the sigma receptor ligand (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine in sympathetic neurons of the mouse isolated hypogastric ganglion.

The actions of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)3-PPP] on sympathetic neurons of the mouse isolated hypogastric ganglion were studied using the current clamp and single electrode voltage clamp techniques. In neurons studied under current clamp (+)3-PPP (10(-5) to 3 x 10(-4) M) evoked a concentration-dependent depolarization, which was fully reversible on washout of the drug. The depolarization was associated with an increase in membrane input resistance. At membrane potentials between -43 and -65 mV the amplitude of the depolarization was inversely related to the membrane potential. (+)3-PPP had no effect on membrane potential at potentials negative to -65 mV. The effect of (+)3-PPP on the M-current was studied in cells voltage clamped at -40 mV and stepped to -60 mV for 300-500 ms. The slow current relaxations seen during and after the voltage step are largely due to the M-current. (+)3-PPP (3 x 10(-5) to 3 x 10(-4) M) inhibited the M-current and produced an inward current in a concentration-dependent manner. (-)3-PPP (3 x 10(-5) M) had similar effects, but was less potent than (+)3-PPP. (+)3-PPP (3 x 10(-5) M) also inhibited the A-current and a calcium-dependent potassium current, but to a lesser degree than the M-current.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Glycine-insensitive desensitization of NMDA responses in cultured mouse embryonic neurons.

The influence of glycine on the desensitization of NMDA-induced currents was studied using cultured embryonic mouse neurons. Although glycine often appeared to reduce desensitization in the whole-cell mode, it had no effect on desensitization in outside-out patches. Various interpretations can be proposed for this discrepancy, such as the presence in intact cells of an intracellular factor regulating desensitization, or the masking of desensitization in intact cells by restricted diffusion of the agonist in the extracellular space. The fact that glycine potentiates the NMDA responses under conditions where it does not regulate desensitization indicates that the potentiation cannot be explained by a reduction of desensitization.

Animals↗
PubMed1990

Activation of mu- and delta-opioid receptors present on the same nerve terminals depresses transmitter release in the mouse hypogastric ganglion.

1. The inhibitory actions of mu- and delta-opioid receptor agonists on the strong, single fibre synaptic input to neurones contained in the mouse hypogastric ganglion have been examined. 2. The opioid agonists [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO, 10 nM-10 microM), morphine (10-30 [D-Ser2,Leu5,Thr6]enkephalin (DSLET, 3 nM-1 microM), [D-Pen2,D-Pen5]enkephalin (DPDPE, 10 nM-10 microM), all depressed the single fibre, all-or-nothing, nicotinic, excitatory synaptic potential (e.p.s.p.) recorded in mouse hypogastric ganglion neurones. U50488H (0.3-1 microM) was without effect. 3. The effect of DSLET, but not that of DAMGO, was reversed by the delta-opioid receptor-selective antagonist, ICI 174864 (0.3 microM). Naloxone (0.3 microM) antagonized the effect of both DSLET and DAMGO. 4. The site of action of the mu- and delta-receptor agonists was on the presynaptic terminals, since at the concentrations which depressed the e.p.s.p. these drugs did not affect the resting membrane potential or input resistance of the postganglionic neurone body, nor did they depress the postganglionic, nicotinic response to exogenously applied acetylcholine. 5. Quantal analysis further confirmed the presynaptic site of action; mu- and delta-opioid receptor agonists decreased the mean number of quanta released per stimulus but did not reduce the mean amplitude of the quantal unit. 6. It was concluded that mu- and delta-opioid receptors were located on the same presynaptic nerve terminals since, in the same neurones, mu- and delta-opioid receptor agonists depressed the same single fibre inputs. 7. The potassium channel blockers barium and quinine, at concentrations known to block opioidactivated somatic potassium conductances, reduced slightly but did not abolish the mu- and delta-opioid receptor-mediated inhibition of the e.p.s.p.

Animals↗
PubMed1990

Competitive antagonists and partial agonists at the glycine modulatory site of the mouse N-methyl-D-aspartate receptor.

1. Kynurenate (Kyn), 7-chlorokynurenate (7-Cl-Kyn), 3-amino-1-hydroxypyrrolid-2-one (HA-966) and D-cycloserine are known to bind to the glycine site that modulates the N-methyl-D-aspartate (NMDA) response of vertebrate central neurones. The effects of these compounds were investigated with patch-clamp and fast-perfusion techniques on mouse cortical neurones in primary culture in an effort to establish whether they act as antagonists, partial agonists and/or inverse agonists of glycine. A fast drug application method allowed the study of both steady-state and transient responses. 2. The analysis of steady-state responses indicates that the main effects of Kyn and 7-Cl-Kyn are those expected from competitive antagonists of glycine, with a dissociation constant of 15 microM for Kyn, and of 0.3 microM for 7-Cl-Kyn. Concentration jumps indicate that at all concentrations of glycine, and in particular in the absence of added glycine, the blockade by Kyn and 7-Cl-Kyn develops at a rate which is close to the rate of dissociation of glycine from its binding site and is independent of antagonist concentration. 3. The main effects of D-cycloserine and of HA-966 are those of partial agonists of high and low efficacy, respectively. In the absence of added glycine, D-cycloserine always produced a potentiation, while HA-966 produced either a potentiation or an inhibition. This can be explained by assuming the presence of a variable level of contaminating glycine. With both D-cycloserine and HA-966, concentration jumps produced biphasic relaxations in which the onset rate of the slow component was, here again, close to the rate of dissociation of glycine from its binding site. 4. These results can be interpreted by assuming that (1) Kyn and 7-Cl-Kyn are competitive antagonists of glycine, (2) HA-966 and D-cycloserine are partial agonists, (3) in the absence of added glycine some glycine is present in the extracellular solution and (4) the response in the total absence of glycine is very small or negligible.

Action Potentials↗
PubMed1989

The effects of vanadate on the yeast Saccharomyces cerevisiae.

Growth of Saccharomyces cerevisiae on non-fermentable medium was more sensitive to inhibition by vanadate than growth on fermentable medium. The frequency of petite mutants increased in cultures grown for 18 hours in fermentable medium containing vanadate. However, oxygen uptake markedly increased in yeast cultures grown in the presence of vanadate, a similar effect being produced by phosphate. It was also found that oligomycin toxicity was relieved by vanadate. These results suggest that vanadate may interact with the mitochondria of S. cerevisiae.

Culture Media↗
PubMed1989

A comparison of the effects of chromate, molybdate and cadmium oxide on respiration in the yeast Saccharomyces cerevisiae.

Growth of Saccharomyces cerevisiae on non-fermentable medium was more sensitive to inhibition by chromate than growth on fermentable medium. Chromate was selectively toxic against oxygen uptake in cells grown in non-fermentable medium and also induced petite mutations. CdO demonstrated similar but lesser effects on growth and respiration. However, molybdate had little toxicity to yeast non-fermentable growth and stimulated oxygen uptake in cells grown in fermentable and non-fermentable media. These results suggest that chromate, a carcinogen, may act more directly against the mitochondria of S. cerevisiae than related chemical species, CdO and molybdate.

Cadmium↗
PubMed1989

An examination of the putative sigma-receptor in the mouse isolated vas deferens.

1. The effects of several ligands which interact with the sigma-binding site were studied on the electrically-evoked (0.1 Hz) neurogenic twitch contractions of the mouse isolated vas deferens. 2. (+)-3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine [+)-3-PPP) (10(-8) - 10(-5) M), inhibited the neurogenic twitch contractions. This inhibitory action was unaffected by naloxone (10(-6)M), idazoxan (10(-6)M), cocaine (10(-6)M) or tyramine (10(-4)-3 x 10(-4)M), but was abolished by the dopamine D2-antagonist, sulpiride (10(-6)M). Therefore, in order to study the potentiating actions of sigma ligands, sulpiride (10(-6)M) was used to prevent any inhibitory actions mediated via dopamine D2-receptors. 3. In the presence of sulpiride (10(-6)M), haloperidol (10(-6)-10(-5)M), (+)-3-PPP (10(-6)-3 x 10(-4) M) and (+)-N-allyl-N-normetazocine [+)-SKF 10,047) (10(-5)-10(-4)M) each reversibly potentiated the neurogenic twitch contractions in a concentration-dependent manner. The rank order of potency was haloperidol greater than (+)-3-PPP greater than (+)-SKF 10,047. 4. The stereoisomers of 3-PPP displayed stereoselectivity with (+)-3-PPP being more potent than (-)-3-PPP. 5. At a concentration that did not potentiate the twitch contractions, (3 x 10(-7)M), haloperidol did not antagonize the potentiating action of (+)-3-PPP (3 x 10(-5)M). 6. 1,3-Di-O-tolyguanidine (DTG) (10(-8)-10(-5)M) had no effect on the amplitude of twitch contractions and did not affect the potentiating action of (+)-3-PPP (10(-5)-3 x 10(-5)M). 7. It is concluded that a-ligands potentiate neurogenic twitch contractions of the mouse isolated vas deferens via a site that is different from the central sigma-binding site.

Animals↗
PubMed1988

Neural function: metabolism and actions of inositol metabolites in mammalian brain.

In the nervous system, a variety of cell types respond to external stimuli through the inositol lipid signalling pathways. The stimulus-coupled sequence of intracellular events has been investigated in a homogeneous model system, the cloned mammalian neural cell line NG115-401L. The neural peptide bradykinin stimulates a rapid production of identified inositol phosphate isomers and an intracellular Ca2+ discharge followed by a persistent plasma membrane influx. The temporal sequence suggests that Ins(1,4,5)P3 or Ins(1,3,4,5)P4 or both may coordinate these events in a neuronal cell, as has been suggested in other cell types. Thapsigargin, an irritant and tumour-promoting plant product, produces calcium transients in the absence of inositol phosphate production, and may provide a new tool for investigating the interactions between inositol phosphates and changes in cellular calcium homeostasis. In the 401L line, high levels of radiolabelled InsP5 and InsP6 have been detected, which has led to the evaluation of their possible occurrence and actions in normal brain. Both InsP5 and InsP6 are produced from a radiolabelled myo-inositol precursor in intact mature brain in a region-specific manner. This suggests that both inositol polyphosphates may be end products of regionally regulated biosynthetic pathways. When microinjected into a nucleus of the brainstem, or iontophoretically applied to the dorsal horn of the spinal cord, both InsP5 and InsP6, but not Ins(1,3,4,5)P4 isomers, appear to be potent neural stimulants. These results suggest that the inositol lipid signalling pathways may generate both intracellular and extracellular signals in brain.

Animals↗
PubMed1987

Flow cytometric quantification of cholesteryl ester-containing "foam" cells. II. Analysis of aortas from cholesterol-fed swine.

We have examined foam cell accumulation in abdominal and thoracic aortic segments of swine with experimentally induced atherosclerosis. Young (less than 1-year-old) male swine were divided into four groups that were fed control, lard (20%), lard (20%) plus cholesterol (1%), and regression (3 months cholesterol-lard followed by 3 months control) diets for 6 months. Aortas were removed from animals and enzymatically dissociated. Foam cells were detected by specifically staining their cholesteryl ester inclusions with the fluorescent dye filipin. Flow cytometry was used to quantify the number of foam cells in each aortic cell suspension. Cholesterol-lard feeding increased serum cholesterol levels 6-fold and induced a substantial increase in both abdominal and thoracic foam cell densities. Lesion development in cholesterol-lard-fed animals, as assessed by macroscopic evaluation of aortas, correlated with foam cell accumulation as determined by flow cytometry. Accumulation of foam cells was extremely variable from animal to animal and did correlate significantly with serum cholesterol but not with serum triglyceride levels. Interestingly, although serum cholesterol levels increased 1.5-fold in swine fed the lard diet, foam cells did not increase significantly as compared to control animals. Animals placed on a control diet following 3 months of the cholesterol-lard diet showed a trend toward lower foam cell densities as compared to animals fed the cholesterol-lard diet for the entire 6 months. Flow cytometric analysis of filipin-stained aortic foam cells provides a new means to evaluate atherosclerotic lesion development.

Animals↗
PubMed1987

Kappa opioid receptor activation depresses excitatory synaptic input to rat locus coeruleus neurons in vitro.

Intracellular recordings were made from neurons of the rat locus coeruleus contained within a brain slice maintained in vitro. When applied to the slice in known concentrations the selective kappa opioid receptor agonist trans-(+)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide methane sulphonate (U50488) (0.01-1 microM) produced a concentration-dependent depression of the excitatory post-synaptic potential evoked by electrical stimulation of afferent inputs to the locus coeruleus. This effect was antagonized by naloxone with an apparent dissociation equilibrium constant (Kd) of 28 nM. U50488 did not completely abolish the EPSP. Over the same concentration range U50488 had no effect on the resting membrane potential, input resistance or action potential waveform of locus coeruleus neurons, nor did U50488 depress the depolarization produced by local application of L-glutamic acid. The mu opioid receptor agonists [D-Ala2, NMe Phe4, Gly-ol5] enkephalin (0.003-1 microM) and [D-Ala2, NMe Phe4, Met(O)5] enkephalinol (0.003-1 microM) caused a membrane hyperpolarization concomitant with a fall in neuronal input resistance. These effects were concentration-dependent and antagonized by naloxone with an apparent Kd of 1.5 nM. Mu agonists also caused a depression of the tetrodotoxin resistant action potential. An in vitro autoradiographic study of [3H]bremazocine binding within the locus coeruleus revealed that, although the majority of binding appears to be to mu sites, a significant proportion was displaceable by unlabelled U50488 and thus represented kappa binding sites. The possibility that kappa opioid receptors may be located pre-synaptically within the locus coeruleus, and that activation of these receptors depresses excitatory synaptic input, is discussed.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

The rise of technology in Chinese hospitals.

Chinese hospitals in the 1980s are in the midst of a technological revolution. Based upon data from several regions in China, this paper describes the political, organizational, economic, and philosophical changes which have accompanied the shift in focus from primary care medicine to high technology tertiary care. The increased authority of physicians, greater contact with the West, and increased funding for medical equipment are key factors in these changes. Although the Chinese state continues to control the administration and financing of most hospitals, the decentralizing reforms of Deng Xiaoping have undermined its ability to effectively plan for, and assess new technology. At present, limited resources prevent most regions from excessive technology acquisition, but the state must rebuild its planning capacity in order to foster rational allocation of scarce medical resources.

Capital Expenditures↗