Retroactive amnesia induced in chicks by the proline analog L-baikiain, without EEG seizures or depression

L-Proline induces retroactive amnesia without causing brain seizures or isoelectric activity. L-Baikiain, a proline analog containing one more carbon atom in the ring and a double-bond, has similar amnestic effects but at one-fourth the dose. Chicks were injected intracerebrally with 5 μl/hemisphere of 150 mM L-biakiain, L-proline, or D-proline, 1 min after one-trial training to suppress the spontaneous peck response to a 3-mm stainless steel bead. The results demonstrate that L-baikiain is an effective retroactive amnestic agent compared to D-proline controls. The amnestic effect induced by 1.5 μmols of L-baikiain is comparable to that found with 6.0 μmols of L-proline in previous experiments. Electrophysiological recording of multiple-unit activity and raw integrated EEG activity showed no seizure spiking or isoelectric activity. No reliable differences in EEG and multiple-unit activity were observed betwen L-baikiain and D-proline injections. We conclude that L-baikiain is approximately 4x more potent than L-proline as an amnestic agent and that both compounds are effective at non-lethal doses which cause no marked electrophysiological changes.     

Cholinergic neurotransmission in retinal spreading depression

Summary Experiments performed to demonstrate the participation of cholinergic synapses in retinal spreading depression (SD) have shown that: (1) acetylcholine (ACh) is liberated during SD, its concentration increasing up to 10 ^-4 mM in the superfusate of one eye cup; (2) the susceptibility of the retina to SD and the velocity of propagation of circling SD are influenced by cholinergic and anticholinergic drugs. ACh 1 mM is effective in eliciting the reaction, whereas d-tubocurarine 0.01 mM and atropine 0.25 mM block this effect. Prostigmine 0.075 mM is able to trigger the reaction and also potentiates the effect of ACh. The velocity of propagation is decreased by ACh 0.25–1.0 mM and prostigmine 0.030 mM, which also potentiate this effect of ACh. Pulses of d-tubocurarine 0.005–0.030 mM and atropine 0.025–0.30 mM decrease the velocity of propagation. However, they block the effect of ACh if they are continuously present in the superfusing solution; (3) the effects of ACh are not blocked by tetrodotoxin 3.19×10^-3 mM.     

Contractile activation and the effects of 2,3-butanedione monoxime (BDM) in skinned cardiac preparations from normal and dystrophic mice (129/ReJ)

(1) Small cardiac myofibrillar preparations were obtained from the right ventricle of normal (129/ReJ) and dystrophic (129/ReJ dy/dy) mice and were chemically skinned in a relaxing solution by exposure to Triton X-100 (3% v/v). (2) The isometric force produced in these skinned cardiac preparations at different sarcomere lengths was measured in solutions of different [Ca²⁺] and ionic strength. The effect of the negative inotropic drug 2,3-butanedione monoxime (BDM), which is known to act at the myofibrillar level was also investigated. (3) The murine cardiac preparation from normal animals was found to develop 50% maximal force at a pCa (=–log₁₀[Ca²⁺]) of 5.59±0.08 and 5.94±0.03 (mean ±SD) under physiological (ionic equivalents concentration, I=154 mM; pH 7.10; [Mg²⁺] 1 mM) and low ionic strength (I=94 mM; pH 7.10; [Mg²⁺] 1 mM) conditions respectively. The isometric force curves were significantly shallower at low ionic strength (Hill coefficient, 1.8±0.1) than at physiological ionic strength (Hill coefficient, 2.6±0.3) and the sarcomere length effect on the force-pCa relation was markedly reduced at lower ionic strength. (4) Increasing BDM concentrations in solutions up to 100 mM reduced the maximum Ca²⁺-activated force of cardiac preparations from normal mice to less than 6% of the control values in a dose dependent fashion. BDM also rendered the cardiac preparations less sensitive to Ca²⁺ by a factor of up to 1.5 in a process which showed saturation at BDM concentrations higher than 15 mM. (5) Cardiac preparations from dystrophic animals compared with those from normal mice were significantly more sensitive to Ca²⁺ under physiological conditions, were more sensitive to the action of BDM at concentrations higher than 15 mM, changed sensitivity to Ca²⁺ less following a change in sarcomere length and in general were less affected by a decrease in ionic concentration. (6) The results indicate that dystrophy in mice affects the characteristics of both the contractile and regulatory systems of cardiac muscle and that BDM directly affects the Ca²⁺-activated contractile response possibly by binding to saturable sites on the myofilaments.     

Involvement of GABA and ACh in retinal spreading depression: Effects of “low calcium — high magnesium” solutions

Summary Experiments have been performed on isolated chick retinas to demonstrate the participation of gabaergic and cholinergic systems in spreading depression (SD). Gamma-aminobutyric acid (GABA) and acetylcholine (ACh) were measured in the effluent solution of superfused retinas. The influence of changes in the concentration of calcium/ magnesium on the release of these neurotransmitters was studied. GABA and ACh are released in the superfusate of retinas during SD. Such release was observed during experimental periods longer than 2 h during which SD was elicited regularly at 15–20 min intervals. Decreasing calcium concentration from 1.0 to 0.5 mM and simultaneously increasing magnesium from 1.0 to 2.0–4.0 mM led to a decrease in GABA and ACh release during SD. Variations in light-scattering and increases in potassium concentration, usually occurring during SD, also decreased when supervising with low calcium/ high magnesium solutions. Lowering calcium concentration to 0.5 mM and increasing magnesium to 2.0 mM eventually turned the tissue refractory to SD. Sometimes a magnesium concentration of 2.0 mM was not effective in blocking SD. However, this blockage could be attained by increasing the concentration of magnesium to 4.0 mM. The effects of low calcium — high magnesium solutions on GABA and ACh release during SD suggests that the release of the substances is at least partially due to synaptic activity. It is not yet possible to establish whether GABA and ACh release is essential for the occurrence of SD. Nevertheless such release suggest that these neurotransmitters could influence the characteristics of SD manifestations in the retina.     

Chelation of intracellular zinc ions affects human sperm cell motility.

The effects of two different zinc chelators, diethyldithiocarbamate (DEDTC) and calcium ethylenediaminetetraacetic acid (EDTA), in full semen samples and 'swim-up' samples were investigated. DEDTC, which crosses cell membranes, and EDTA, which does not cross cell membranes, were added to semen samples in different concentrations. Sperm cell motility parameters were assessed by computer-assisted semen analysis (CASA). It was found that very small concentrations (0.01 mM) of DEDTC immobilized the sperm cells within 80 min, while EDTA had no depressing effect at the concentrations used. In full semen samples EDTA enhanced straight line velocity (VSL) at concentrations of 1.0 and 0.5 mM; this effect was not found at higher concentrations. It is suggested that intracellular mitochondrial zinc ions play a crucial role for sperm cell motility, while loosely bound or free zinc ions in the seminal plasma exert a secondary role on human sperm cell motility.     

Azide sensitive components of potassium efflux as influenced by the external sodium concentration

Summary Sodium azide at concentrations <–1.0 mM was capable of stimulating potassium efflux from frog sartorius muscles with no significant influence on the intracellular sodium content. At concentrations >–2.0 mM, azide produced a continuously increasing rate of potassium loss which resulted in a net loss of intracellular potassium. This effect was mimicked at low azide concentrations (<–1.0 mM) in the presence of 10^–5 M strophanthidin or 1.0 mM sodium cyanide. It was independent of the intracellular sodium content, but dependent on the external sodium concentration. While increasing concentrations of azide produced incremental increases in the rate of potassium loss in sodium-reduced Ringer's solution, the continuously increasing rate of loss and strophanthidin sensitivity was absent. It is concluded that the biphasic effect of azide on potassium efflux in skeletal muscle resulted from the interaction of this agent with at least two cellular processes, one of which was dependent on the external sodium concentration.     

Modulation of spreading depression by changes in extracellular pH

Spreading depression (SD) and related phenomena have been implicated in hypoxic-ischemic injury. In such settings, SD occurs in the presence of marked extracellular acidosis. SD itself can also generate changes in extracellular pH (pH(o)), including a pronounced early alkaline shift. In a hippocampal slice model, we investigated the effect of interstitial acidosis on the generation and propagation of SD in the CA1 stratum radiatum. In addition, a carbonic anhydrase inhibitor (benzolamide) was used to decrease buffering of the alkaline shift to investigate its role in the modulation of SD. pH(o) was lowered by a decrease in saline HCO(3)(-) (from 26 to 13 to 6.5 mM at 5% CO(2)), or by an increase in the CO(2) content (from 5 to 15% in 26 mM HCO(3)(-)). Recordings with pH microelectrodes revealed respective pHo values of 7.23 +/- 0. 13, 6.95 +/- 0.10, 6.67 +/- 0.09, and 6.97 +/- 0.12. The overall effect of acidosis was an increase in the threshold for SD induction, a decrease in velocity, and a shortened SD duration. This inhibition was most pronounced at the lowest pH(o) (in 6.5 mM HCO(3)(-)) where SD was often blocked. The effects of acidosis were reversible on return to control saline. Benzolamide (10 microM) caused an approximate doubling of the early alkaline shift to an amplitude of 0.3-0.4 U pH. The amplified alkalosis was associated with an increased duration and/or increased velocity of the wave. These effects were most pronounced in acidic media (13 mM HCO(3)(-)/5% CO(2)) where benzolamide increased the SD duration by 55 +/- 32%. The initial velocity (including time for induction) and propagation velocity (measured between distal electrodes) were enhanced by 35 +/- 25 and 26 +/- 16%, respectively. Measurements of [Ca(2+)](o) demonstrated an increase in duration of the Ca(2+) transient when the alkaline shift was amplified by benzolamide. The augmentation of SD caused by benzolamide was blocked in media containing the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid. These data indicate that the induction and propagation of SD is inhibited by a fall in baseline pH characteristic of ischemic conditions and that the early alkaline shift can remove this inhibition by relieving the proton block on NMDA receptors. Under ischemic conditions, the intrinsic alkalosis may therefore enable SD and thereby contribute to NMDA receptor-mediated injury.     

Acetazolamide and renal ammoniagenesis.

The effect of acetazolamide on ammonia-producing enzyme systems was determined in vitro at concentrations comparable to those which have been shown to abolish ammonium excretion in vivo. No change in the activity of glutaminase or gamma-glutamyl transpeptidase could be observed at concentrations up to 0.2 mM acetazolamide, and concentrations up to 1 mM were without effect on D-glutamyltransferase activity. Therefore, the effect of acetazolamide to abolish ammonium excretion cannot be explained by an action of the drug to inhibit ammoniagenesis.     

Effects of N-acetyl-L-cysteine and glutathione on antioxidant status of human serum and 3T3 fibroblasts

The effectiveness of several sulfhydryl compounds in the treatment of paraquat intoxication has been previously tested based on their antioxidant ability. However, practical guidelines for their clinical use remain to be determined. As a preliminary pharmacokinetic study on sulfhydryl compounds, we attempted to establish the optimal concentration of N-acetyl-L-cysteine, glutathione, superoxide dismutase, and catalase. We measured the antioxidant effect of these antioxidants in normal pooled plasma and on intracellular reactive oxygen species (ROS) induced by paraquat. N-acetyl-L-cysteine begins to suppress the production of ROS in plasma at concentrations as low as 5 mM, with the suppression being maximal at 40 mM. In the same way, glutathione increased the total antioxidant status in plasma at concentrations of 5-40 mM in a dose-dependent manner. Complete suppression of ROS in plasma induced by exposure to 500 micro M paraquat for 40 min was observed when using 40 mM N-acetyl-L-cysteine and 5 mM glutathione. These concentrations are comparable with 50 units of catalase, which reduced ROS at concentrations of 5-100 units. Further pharmacokinetic study into the systemic administration of these antioxidants is necessary, using effective concentrations of 5-40 mM for both N-acetyl-L-cysteine and glutathione, and 1-50 units of catalase.     

Block of receptor response in the stretch receptor neuron of the crayfish by gadolinium.

The trivalent lanthanide gadolinium was found to block the mechanotransducer response in the stretch receptor neuron of the crayfish. At normal calcium concentration (13.5 mM) a 50 per cent block of the receptor current was found at 395 +/- 59 (mean +/- SD) microM gadolinium. At a calcium concentration of 1.35 mM a 50 per cent block of the receptor current was obtained at 103 +/- 14 (mean +/- SD) microM gadolinium. The potential activated potassium current was also affected by gadolinium. At 200 microM the amplitude of the peak outward current as a result of a 90 mV positive potential step was decreased by about 40 per cent. The fast inward sodium current was decreased less than 10 per cent by gadolinium. It is concluded that in the crayfish stretch receptor gadolinium blocks the receptor current, reflecting block of stretch-activated channels, but at higher concentrations than have been described for other stretch-activated channels. In addition the outward rectifier potassium current is also blocked reflecting a block of potassium channels.     

Effects of 3‘, 5’-Cyclic Adenosine Monophosphate, 5-Hydroxy-tryptamine,Noradrenaline and Theophylline on the Simultaneous Release of Peroxidase and Amylase from the Guinea Pig Submanibular Gland

Noradrenaline (NA), 5-hydroxytryptamine (5-HT) and N⁶,2-0′-dibutyryl cyclic adenosine monophosphate (DBcAMP) induced a parallel discharge of peroxidase and amylase from the guinea pig submandibular gland in vitro. Theophylline alone, at a concentration of 5 mM, had only little effect on enzyme secretion, but it markedly potentiated the effects of noradrenaline, 5-HT and DBcAMP at submaximal concentrations. Adenosine-3′-monophosphoric acid (3′-AMP) and adenosine-5′-monophosphoric acid (5′-AMP) were without effect on enzyme secretion. Maximal effects of NA and DBcAMP on enzyme release were obtained at concentrations of 0.01 mM and 3 mM respectively. Dose-response curves for the stimulation of peroxidase and amylase release by 5-HT revealed that this amine was a potent secretagogue at the concentrations of 0.1 and 0.3 mM but was less effective at higher concentrations. It is concluded that peroxidase and amylase are simultaneously secreted from the guinea pig submandibular gland, and that the release of both enzymes is mediated via cyclic AMP.     

Myo‐Inositol: a marker of reactive astrogliosis in glial tumors?

In a prospective study, two-dimensional (1)H-MRS with TE of 30 ms was performed before surgery in 56 patients with glial brain tumors. Concentrations of myo-inositol (MI), trimethylamine (TMA) and creatine/phosphocreatine (tCr) were evaluated for the whole tumor and scaled to the normal-appearing contralateral brain tissue. To assign changes in MI to specific tissue pathology, the normalized peak and mean concentrations of MI were correlated with TMA and tCr concentrations. TMA is accepted as a marker of proliferating tumor tissue, and tCr might be a marker of reactive astrogliosis. The mean and peak concentrations of MI and tCr correlated positively (r = 0.7), but not the concentrations of MI and TMA. The absolute concentration of MI was significantly increased in all tumor tissues (5.55 +/- 2.92 mM; mean +/- SD) compared with the normal-appearing white matter (4.33 +/- 1.22 mM, p = 0.005), with the highest concentrations for gliomatoses (n = 10) and grade II oligoastrocytomas (n = 3). Significant differences (P = 0.004) between low- and high-grade astrocytomas were found for TMA (1.67 +/- 0.32 mM and 2.65 +/- 0.86 mM, respectively), but not for MI (5.92 +/- 1.98 mM and 5.49 +/- 3.27 mM, respectively). As increased MI and tCr concentrations were found in gliomatosis and other cerebral diseases associated with marked astrogliosis, this process may also be responsible for the observed changes in MI in other glial tumors.     

Cytotoxicity of ionophore A23187 for basophils and other human blood cells.

The calcium ionophore A23187(A23) at concentrations exceeding 1 microgram/ml has been shown to be progressively cytotoxic for human blood basophils, neutrophils, lymphocytes, and erythrocytes. Toxicity to basophils was considered to be manifested by the increasing inability of 2-deoxyglucose (2DG) to inhibit histamine release (HR) at increasing concentrations of A23. The toxicity to neutrophils and lymphocytes was demonstrated by decreased lactate production (LP) after incubation with A23 of Ficoll-Hypaque fractions greatly enriched in each respective cell type. Red cells present in dextran-sedimented leukocytes were increasingly susceptible to lysis during washing subsequent to exposure to increasing concentrations of A23. A concentration of 4 microgram A23/ml, which is cytotoxic at 37 degrees C, produced optimal and noncytotoxic HR at 22 degrees C. It was possible to reduce A23 concentrations required for optimal HR by increasing Ca++ from 0.6 to 3 mM.     

Potassium distribution and membrane potential of sensory neurons in the leech nervous system

The intracellular K activity (aKi) and membrane potential of sensory neurons in the leech central nervous system were measured in normal and altered external K+ concentrations, [K+]o, using double-barreled, liquid ion-exchanger microelectrodes. In control experiments membrane potential measurements were made using potassium chloride-filled single-barreled microelectrodes. All values are means +/- SD. At the normal [K+]o (4 mM) the mean aKi of all cells tested was 72.6 +/- 10.6 mM (n = 40) and the average membrane potential was -47.3 +/- 5.2 mM (n = 40). When measured with single-barreled microelectrodes, the membrane potential averaged -45.3 +/- 2.9 mV (n = 12). Assuming an intracellular K+ activity coefficient of 0.75, the intracellular K+ concentration of sensory neurons would be 96.8 +/- 14.1 mM). With an extracellular K+ concentration of 5.8 mM in the intact ganglion compared to the K+ concentration of 4 mM in the bath, the K+ equilibrium potential was -71.5 mV. When the ganglion capsule was opened, the extracellular K+ concentrations in the ganglion were similar to that of the bathing medium and the calculated K+ equilibrium potential was -81 mV. The membrane of sensory neurons depolarized following the changes to elevated [K+]o (greater than or equal to 10-100 mM), whereas aKi changed only little or not at all. At very low [K+]o (0.2, 0 mM) aKi and membrane potential showed little short-term (less than 3 min) effect but began to change after longer exposure (greater than 3 min). Reduction of [K+]o from 4 to 0.2 mM (or 0 mM) produced first a slow, and then a more rapid decrease of aKi and membrane resistance, accompanied by a slow membrane hyperpolarization. Following readdition of normal [K+]o, the membrane first depolarized and then transiently hyperpolarized, eventually returning slowly to the normal membrane potential.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of 4-aminopyridine on release of noradrenaline from the perfused cat spleen by nerve stimulation.

1. 4-aminopyridine (4-AP, 1 mM) increased noradrenaline (NA) output from the perfused cat spleen at 5 Hz by about fivefold. Enhancement of NA release by 4-AP was reversible. Output of NA induced by potassium was not affected. 2. NA output was doubled at low concentrations (0.1--0.3 mM) of 4-AP, but maximal effect was obtained at 1--3 mM. At 10 mM, it induced spontaneous release of NA which was insensitive to calcium. 3. Insignificant outputs obtained at 5 Hz in 0.1 and 0.3 mM calcium-Krebs solution were markedly enhanced by 4-AP. 4-AP enhanced release at all calcium concentrations up to 5 mM, but maximum output was obtained at 2.5 mM. 4. 4-AP at pH 8.5 was more effective in enhancing NA release than at pH 7.4. 5. 4-AP increased the recovery of intra-arterially infused NA from the control 26 to 47%. 6. 4-AP did not affect release of catecholamines (CA) from the perfused cat adrenal gland by acetylcholine (ACh). 7. It is suggested that 4-AP inactivates potassium current in sympathetic nerves and prolongs the duration of the action potential, thereby allowing a greater influx of calcium ions into the neurone to enhance release of NA.     

The effects of pentoxifylline on rat erythrocytes of different age

Age-separated rat erythrocytes were exposed to pentoxifylline, a dimethylxanthine derivative which increases erythrocyte deformability. A comparison of drug-induced effects in young and old erythrocytes yielded age-specific alterations in: (1) accumulation of intracellular Ca2+; (2) membrane protein phosphorylation; (3) ATP concentrations; and (4) membrane associated protein kinase activity. The effect of Ca2+ accumulation and membrane protein phosphorylation appears to be biphasic. Low drug concentrations (0.5-2.5 mM) reduced intracellular Ca2+ and increased membrane protein phosphorylation, whereas higher concentrations (4.0-5.0 mM) increased Ca2+ levels and reduced membrane protein phosphorylation. Young cells exhibited increased ATP levels over the whole range of pentoxifylline tested; however, older erythrocytes demonstrated higher ATP levels at 5.0 mM drug only. Membrane-associated protein kinase activity was enhanced 10% in young erythrocytes at 1.0 mM pentoxifylline and decreased to 30% of control values at 4.0 and 5.0 mM drug. Protein kinase of old erythrocytes exhibited gradual inhibition over the entire drug concentration range. In general, younger erythrocytes appear to be more responsive to pentoxifylline exposure. Based on these studies, it appears that the ageing of the erythrocyte and loss of deformability in vivo may be a consequence of increased Ca2+ entry into the cell.     

Interstitial glucose concentration in insulin-resistant human skeletal muscle: influence of one bout of exercise and of local perfusion with insulin or vanadate

The present study investigated the changes occurring in interstitial metabolite concentrations and blood flow in insulin-resistant human skeletal muscle during the post-exercise recovery period following a single 2-h bout of one-legged exercise. In addition, the effect of microdialysis perfusion with insulin or the insulin-mimetic trace element vanadate was explored. Eight microdialysis catheters, four in each leg, were inserted in the quadriceps femoris muscle of nine insulin-resistant obese male subjects 2 h following exercise. Two catheters in each leg were perfused at 0.2 microl/min for metabolite determinations and two at 1.33 microl/min for the determination of blood flow. Samples were collected until 9 h after the end of exercise had passed. The interstitial glucose concentration (mean +/- SD) was significantly lower in the exercised (2.8 +/- 1.3 mM) than in the rested leg (3.7 +/- 0.9 mM), P = 0.001, a difference that lasted at least 8 h after the exercise bout. On the other hand, blood flow was not different in the two legs. Microdialysis perfusion with insulin (14 mU/ml) or sodium metavanadate (100 mM) decreased the interstitial glucose concentration (P = 0.001) in both the exercised and rested leg. With vanadate, this decrease was similar in the exercised (-69%) and the rested leg (-71%), whereas insulin had a larger effect in the exercised leg (-29 vs. -6.9%), P = 0.05. This study shows that the interstitial glucose concentration in insulin-resistant skeletal muscle is markedly decreased for several hours following a single exercise session. This is in accordance with recent findings in healthy subjects. This change is accompanied by an increased insulin effect on the interstitial glucose concentration. The effect of vanadate was not decreased in insulin-resistant human skeletal muscle and was not augmented by exercise.     

Opioid receptors on bulbospinal respiratory neurons are not activated during neuronal depression by clinically relevant opioid concentrations

Opioids depress the activity of brain stem respiratory-related neurons, but it is not resolved whether the mechanism at clinical concentrations consists of direct neuronal effects or network effects. We performed extracellular recordings of discharge activity of single respiratory neurons in the caudal ventral respiratory group of decerebrate dogs, which were premotor neurons with a likelihood of 90%. We used multibarrel glass microelectrodes, which allowed concomitant highly localized picoejection of opioid receptor agonists or antagonists onto the neuron. Picoejection of the mu receptor agonist [d-Ala(2), N-Me-phe(4), gly-ol(5)]-enkephalin (DAMGO, 1 mM) decreased the peak discharge frequency (mean +/- SD) of expiratory neurons to 68 +/- 22% (n = 12), the delta(1) agonist d-Pen(2,5)-enkephalin (DPDPE, 1 mM) to 95 +/- 11% (n = 15), and delta(2) receptor agonist [d-Ala(2)] deltorphin-II to 86 +/- 17% (1 mM, n = 15). The corresponding values for inspiratory neurons were: 64 +/- 12% (n = 11), 48 +/- 30% (n = 12), and 75 +/- 15% (n = 11), respectively. Naloxone fully reversed these effects. Picoejection of morphine (0.01-1 mM) depressed most neurons in a concentration dependent fashion to maximally 63% (n = 27). Picoejection of remifentanil (240-480 nM) did not cause any significant depression of inspiratory (n = 11) or expiratory neurons (n = 9). 4. Intravenous remifentanil (0.2-0.6 microg.kg(-1).min(-1)) decreased neuronal peak discharge frequency to 60 +/- 12% (inspiratory, n = 7) and 58 +/- 11% (expiratory, n = 11). However, local picoejection of naloxone did not reverse the neuronal depression. Our data suggest that mu, delta(1), and delta(2) receptors are present on canine respiratory premotor neurons. Clinical concentrations of morphine and remifentanil caused no local depression. This lack of effect and the inability of local naloxone to reverse the neuronal depression by intravenous remifentanil suggest that clinical concentrations of opioids produce their depressive effects on mechanisms upstream from respiratory bulbospinal premotor neurons.     

The “In Vitro” Effects of Lithium on the Immune System

This study has examined the “in vitro” effects of Lithium Carbonate on the immune system at low (10^-3, 10^-2mM) and therapeutic (0.5–1.5 mM) concentrations. Lithium, in the presence of a range of mitogens, was found to increase the incorporation of ³H-thymidine into peripheral blood mononuclear (PBM) cells. At concentrations > 1 mM IL2 production was also enhanced. Lithium was also found to increase IgG and IgM production - an estimate of B cell function, the effects being greatest at concentrations within the therapeutic range. However at these levels Lithium inhibited cAMP production.

Whether Lithium acts individually on these processes or whether one reaction is merely the result of another is unclear at present.     

Effects of 4-aminopyridine and tetraethylammonium on the depolarization by GABA of cultured satellite glial cells

4-Aminopyridine (4-AP) which selectively blocks K+-conductance of excitable membranes, reversibly abolished the depolarization by gamma-aminobutyric acid (GABA) of cultured satellite glial (SG) cells, but did not or only slightly affect the action of GABA on dorsal root ganglion (DRG) neurons. It is therefore suggested that the depolarization of glial cells by GABA is an indirect effect due to the accumulation of K+ which is released from adjacent neurons during their depolarization by the amino acid. Tetraethylammonium (TEA) had no effect on the GABA depolarization at a concentration of 15 mM but produced a slight reduction at higher concentrations (60--70 mM).