In vitro activity of the aryl-fluoroquinolones A-56619 and A-56620 and evaluation of disk susceptibility tests

The activity of two new quinolones, A-56619 and A-56620, was compared in vitro to that of norfloxacin and ciprofloxacin against 6,699 bacterial isolates in four separate clinical laboratories. The overall percentage of strains susceptible to designated concentrations were as follows: 99.1% for norfloxacin (MIC4.0 g/ml), 96.1% for ciprofloxacin (MIC1.0 g/ml), 96.8% for A-56620 (MIC 2.0 g/ml) and 96.1% for A-56619 (MIC 4.0 g/ml). For disk diffusion susceptibility tests 10 g A-56619 disks are tentatively recommended with interpretive standards of 18mm for susceptibility and 13mm for resistance; 5 g A-56620 disks may be used with tentative standards of 19mm for susceptibility and 14mm for resistance.     

Isoproterenol and GTPγS inhibit L-type calcium channels of differentiating rat skeletal muscle cells

Summary In adult skeletal muscle, G-proteins have been shown to modulate the calcium channels both directly and through a cAMP-dependent phosphorylating mechanism. We have investigated the action of G-proteins on the L-type calcium current in cultured rat muscle cells (myoballs) under voltage clamp in whole cell or perforated patch modes. Intracellular photolytic release of 200 M GTPS inhibited the L-type calcium current. Inclusion of 500 M uncaged GTPS in the patch pipette in the whole cell configuration reduced the calcium current by a similar amount. Under perforated patch conditions external application of 10 M of the -adrenergic agonist isoproterenol also reduced the calcium current. Pretreatment of the cells with pertussis toxin reversed the effect of GTPS and removed that of isoproterenol. We conclude that rat myoballs contain -adrenergic receptors that inhibit the L-type calcium current, and that this inhibition is mediated by a pertussis toxinsensitive G-protein.     

Activity of trimethoprim/ sulfamethoxazole plus polymyxin B against multiresistantStenotrophomonas maltophilia

The inhibitory activity of eight antibiotics and the inhibitory and bactericidal activities of combinations of trimethoprim/sulfamethoxazole (TMP/SMX) plus three fixed concentrations of polymyxin B (0.01 g/ml, 0.1 g/ml and 0.5 g/ml) against 30 multiresistant strains ofStenotrophomonas maltophilia were tested. Polymyxin B at 0.01 g/ml modified the inhibitory activity of TMP/SMX against only 40% of strains. At 0.1 g/ml and 0.5 g/ml, polymyxin B enhanced the inhibitory activity of TMP/SMX activity against all strains. Polymyxin B enhanced the bactericidal activity of TMP/SMX only at concentrations near the minimum inhibitory concentration of polymyxin B alone.     

Mechanisms underlying facilitation by dopamine of ATP-activated currents in rat pheochromocytoma cells

Mechanisms underlying facilitation by dopamine of extracellular adenosine 5-triphosphate (ATP)-activated current were investigated in rat pheochromocytoma PC12 cells using the whole-cell voltage-clamp techniques. Dopamine (10 and 100 M) augmented the peak amplitude of an inward current elicited by ATP (3–100 M). The activation time course of the ATP-evoked current was accelerated by dopamine; the presence of 10 M dopamine shifted the dependence of activation rate constants on the concentration of ATP toward a lower concentration range two fold. Dopamine also accelerated the inactivation and the deactivation, which was determined from the current decay upon washout of ATP. Intracellular mediators responsible for the dopamine-induced facilitation was estimated by loading various compounds in patch pipettes. Facilitation was not observed when K-252a (1 M), a protein kinase inhibitor, was included in the intracellular solution. In addition, facilitation was also attenuated by intracellular adenosine 5-O-(thiotriphosphate)tetralithium salt (ATPS (1 mM) or --methylene ATP (1 mM). Inclusion of adenosine 3, 5-cyclic monophosphate sodium salt (cAMP, 100 M), guanosine 3,5-cyclic monophosphate sodium salt (cGMP, 100 M), 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 M) or phorbol-12,13-dibutylate (1 M) in the intracellular solution did not affect the facilitation. Guanonsine 5-O-(thiotriphosphate)tetralithium salt (GTPS, 500 M) or guanosine 5-O(2-thiodiphosphate)-trilithium salt (GDPS, 500 M) did not modify the facilitation either. The results suggest that dopamine augments the ATP-activated inward current by facilitating association of ATP to its binding site, and that the augmentation may be mediated through some protein kinase which is different from cyclic-nucleotide-dependent protein kinases or protein kinase C.     

Beeinflussung des post-asphyktischen Wiederaufbaues der Adeninnucleotide in Kaninchenherzenin vivo durch Substratangebot

Zusammenfassung Die Möglichkeit einer Beschleunigung der langsamen postanaeroben Erholung im Status der myokardialen Adeninnucleotide durch ein methodisch einfach durchführbares kontinuierliches Angebot von Substraten, die zum Aufbau von Nucleotiden bedeutungsvoll sein könnten, wurde unterin vivo-Bedingungen am Herzen des Kaninchens anhand von Bestimmungen der Gewebsgehalte von Metaboliten und Substraten des Adenylsäure-Phosphokreatin-Systems und des Glykolysecyclus geprüft. Als anaerobe Belastung diente eine Serie von 4 Asphyxien von 1 mal 3 min und 3 mal 2,5 min Dauer mit zwischenzeitlichen Erholungspausen von 10 min Dauer. Nach Abschluß der raschen Erholungsvorgänge im Herzstoffwechsel wurden die Substrate oder physiologische NaCl-Lösung bis zu einer post-asphyktischen Erholungsdauer von 5 Std in die V. cava sup. oder in das linke Herzohr infundiert. Die Infusion von Bausteinen zurde novo-Synthese des Purinkörpers mit Glycin (6 mol/min), Glutamin (6 mol/min), Asparaginsäure (6 mol/min), Folsäure (2 mol/min), Ameisensäure (0.04 mol/min), Oxalessigsäure (6 mol/min) und Ribose (12 mol/min) und die Infusion von Adenin+Ribose (0.6 bzw. 12 mol/min+12 mol/min) und von Inosin (20 mol/min) resultierte nicht in einem beschleunigten Wiederaufbau der myokardialen Adeninnucleotide; die Ursache wird in einem Mangel an aktivierter Ribose und im Fehlen notwendiger Enzyme im Kaninchenherzmuskel gesehen. Das Angebot von Adenosin (7,5 mol/min) resultierte in einer starken Beschleunigung des post-asphyktischen Wiederaufbaus der Adeninnucleotide und in einer Erhöhung des ATP-Gehaltes und der Summe der Adeninnucleotide um 35 bzw. 39% über die Norm.Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Mechanism of modulation of single sodium channels from skeletal muscle by the β 1-subunit from rat brain

We studied the molecular mechanism of the rat skeletal muscle -subunit (_I) gating kinetics modulation by the brain ₁-subunit by heterologous expression of single sodium channels from _I and ₁ in Xenopus laevis oocytes. Coexpression of ₁ reduced mean open time at –10 mV to 21% when compared to channels expressed by _I alone. Channels formed by _I exerted multiple openings per depolarization, which occurred in bursts, in contrast to the channels formed by the _I/₁ complex that opened in average only once per depolarizing voltage pulse. Macroscopic current decay (mcd), as evidenced by reconstructed open probability vs. time , was greatly accelerated by ₁, closely resembling mcd of sodium currents from native skeletal muscle. Generally was larger for channels expressed from the pure _I subunit.From our single channel data we conclude that ₁ accelerates the inactivation process of the sodium channel complex.     

The effect of phosphatase inhibitors and agents increasing cyclic-AMP-dependent phosphorylation on calcium channel currents in cultured rat dorsal root ganglion neurones: interaction with the effect of G protein activation

Ca²⁺ channel currents have been recorded in cultured rat dorsal root ganglion neurones. The amplitude of I _Ba(GTPS), recorded in the presence of GTP[S] (200 M) in the patch pipette solution, is enhanced by external application of forskolin (10 M), and there is an increase in the proportion of the rapidly activating component of the current. When forskolin (1 M) is present in the bathing solution at the start of recording, or when 8-bromocyclic AMP (100 M) is present in the patch pipette solution, the amplitude and rate of activation of I _Ba(GTPS) are also increased compared to control I _Ba(GTPS). The effect is mimicked by internal application of a 5 M solution of a phosphopeptide fragment of inhibitor 1 (I1PP), which inhibits phosphatase 1. The enhancement of I _Ba(GTPS) caused by I1PP is not additive with that due to forskolin. Furthermore, the enhancement due to I1PP is reversibly lost when the holding potential is shifted from –80 mV to –30 mV, as was the enhancement due to forskolin and 8-bromocyclic AMP. I1PP also produced a less marked stimulation of the control Ca²⁺ channel current in the absence of G protein activation. The results suggest that phosphorylation regulates the interaction between calcium channels and G proteins in these neurones, and that phosphatase 1 is tonically active to dephosphorylate the relevant protein(s).     

Bradykinin Antagonizes the Effects of α-Thrombin

-Thrombin (AT) and bradykinin (BK) are endogenous mediators that are released during an inflammatory response, and could have a synergistic effect on endothelial permeability. Human umbilical vein endothelial cells (HUVEC) were grown on Transwell membranes and then tested for alterations in permeability to fluorescein isothiocyanate-labeled human serum albumin. Addition of 1M AT produced a significant increase in the permeability coefficient at 30 minutes from control levels of 1.59 × 10^–6 cm/sec to 4.92 × 10^–6 cm/sec. BK (1M) produced a similar increase to 4.46 × 10^–6 cm/sec. For both compounds, permeability remained elevated for 90 minutes. Pre-treatment of the HUVEC with the bradykinin receptor antagonist, Na-adamantaneacetyl-bradykinin (NA-BK) (1M), prior to addition of AT, reduced the AT permeability coefficient to 2.69 × 10^–6 cm/sec. Addition of NA-BK (1 M) for 5 minutes, then BK (1 M) for 5 minutes, inhibited the effect of BK and of AT (1 M) on permeability, decreasing the permeability coefficient of the endothelial monolayer to control levels (1.62 × 10^–6 cm/sec). AT (1 M) increased HUVEC intracellular calcium mobilization, as monitored by FURA-2, to 245 nM from control (70 nM), however, pre-treatment with either BK or the bradykinin receptor antagonist decreased the AT induced intracellular calcium mobilization compared to AT alone. Pre-treatment of the HUVEC with bradykinin (1 M) for 2 minutes also inhibited the effects of -thrombin (1 M) on f-actin distribution examined by BODIPY-phallodin staining and increased the clotting times for an -thrombin dependent fibrinogen to fibrin clotting assay. However, incubation of bradykinin (1 M) with -thrombin (1 M) for either 10 minutes or 100 minutes produced no detectable hydrolysis products. These data strongly suggest that the inflammatory mediators -thrombin and bradykinin when released together, rather than being synergistic, are antagonistic.     

Z-line structural diversity in frog single muscle fiber in the passive state

The structural changes of the Z-line between small square net (ss) and basket weave (bw) cross-sectional patterns were examined using intact single fibers and mechanically skinned fibers in the passive state to determine if the pattern is related to the sarcomere length (SL) and if the pattern undergoes a reversible transition in low- and high-osmotic medium.Frog single fibers were isolated from the anterior tibial muscle in Ringer's solution. Entirely or partially skinned single fibers were prepared in relaxing solution (also called low-osmotic medium).The high osmotic medium contained 10% polyvinylpyrrolidone (PVP) in relaxing solution.The sarcomere length (SL) of each fiber was measured directly by use of a laser beam or indirectly from electron micrographs with use of a correction factor. The ss and bw forms in cross sections were quantified by analysis of electron micrographs. The results show that the structural change of Z-line occurs around bw 2.3–2.4m ss (n = 25) and bw 3.1–3.2m ss (n = 13) in intact single fibers and skinned fibers, respectively. With the quick freeze-freeze substitution method, an intact single fiber with a SL of 2.35m showed almost 100% of ss form. The structural transition in cross section was also confirmed in four partially skinned fibers, where patterns went from mostly ss form (intact portion) to mostly bw form (skinned portion) at the SL between 2.40 to 3.20m.The reversibility of the change between ss and bw was proved by using low- and high-osmotic medium. The transition and reversion of cross-sectional patterns both occur in the passive state.     

Expansion of CD14+CD16+Monocytes in Critically Ill Cardiac Surgery Patients

We have asked whether critically ill cardiac valve surgery patients identified by a high APACHE II score exhibit an increase in the number of proin-flammatory CD14⁺ CD16⁺ monocytes. A group of 12 patients was studied over a period of 5 days post cardiac valve surgery for changes in blood monocyte populations. Patients were selected on day 1 post surgery to either be in good clinical condition (APACHE II Score of 14; N = 9) or to be critically ill (APACHE II score of 24; N = 3). The 14 patients had an uneventful course and could leave the ICU after 2–3 days. Among the 24 patients two showed a decrease of the score to 14 within the 5 days of observation and they could leave the ICU thereafter. One 24 patient (patient #2) had a persistently high score and finally died on day 28. Analysis of blood monocytes on day 1 post surgery revealed that the 14 patients had normal values of CD14⁺CD16⁺ monocytes (44 ± 9/l). By contrast the 24 patients had increased values of these cells with 243 ± 106 cells per 1 on day 1. The numbers of CD14⁺CD16⁺ monocytes returned to the control range over the 5 days of observation in 2 of the 24 patients concomitant with the improvement of the APACHE II score. CD14⁺CD16⁺ monocytes remained, however, at a high level in patient #2, the patient with persistently high APACHE II score.     

A comparison of isometric force,maximum power and isometric heat rate as a function of sarcomere length in mouse skeletal muscle

The isometric force, maximum power and isometric heat rate have been measured at different sarcomere lengths (SL) between 1.40 and 3.63 m in two types of mouse muscle, soleus and omohyoideus, at 25°C. The SL force relationship is different in the two muscles. At a SL above optimum filament overlap, 2.44 m in omohyoideus muscles, maximum power declined while isometric force remained high. In soleus muscles this occurred above a SL of 2.33 m. In parallel experiments, the isometric heat rate declined linearly with increasing SL above 2.33 m in soleus muscles, while isometric force remained closer to its maximum. At short SL, between 2.33–1.75 m in soleus and 2.44–2.15 m in omohyoideus, maximum power remained at or near its maximum value as did heat rate (soleus) while isometric force fell. In both muscles at SL greater than optimum for force development maximum power output (unlike force) is proportional to filament overlap. The variation in heat rate over this SL range can be described as the sum of a constant rate and a rate proportional to filament overlap. These observations are compatible with the idea that maximum power and heat rate are less affected by non-uniformities in SL than is force.     

Interferon (type-α and γ) production by fresh and cryopreserved human mononuclear cells

Summary A comparative study of interferon (IFN) production (type- and ) was carried out using Ficoll-hypaque purified fresh and cryopreserved mononuclear cells from eight normal healthy individuals. Newcastle disease virus-NDV (R₂B strain) was used as an inducer for type- and Staphylococcal enterotoxin-A-(SEA) for type-IFN production. There was no significant difference between the titres of type- and -IFN and lymphocyte subpopulations of fresh and cryopreserved mononuclear cells studied under identical conditions.     

Skull radiograph measurements of normals and patients with basilar impression; use of Landzert's angle

Summary One hundred normal lateral skull radiographs were studied and those of ten patients with basilar impression attending Kenyatta Hospital, Nairobi. The mean shortest distance of the odontoid tip to McGregor's basal line was 1.2±2.28 mm below the basal line (range 6 mm below to 3 mm above basal line), in normals and 9±2.7 mm (6–14 mm) above basal line in patients. The mean basal angle was 113±7 (102–133) in normals and 122±6 (113–125) in patients. The mean nasion-basion-opisthion angle was 162±4 (154–169) in normals and 178±5 (173–185) in patients. The mean total length of clivus was 48±3.7 mm (43–56 mm) in normals and 44±6.6 (36–48 mm) in patients group. The mean median diameter of the foramen magnum was 39±5 mm (30–48 mm), atlas 21±3 mm (18–25 mm) axis 18±3 mm (14–23 mm), third cervical vertebra 16±2 mm (13–22 mm) in normals and in patients: 39±4 mm (36–45 mm), atlas 23±6 (l5–30 mm) axis 19±4 mm (16–25 mm), third cervical vertebra 16±3 (14–20). There was a significant difference in the position of the odontoid tip and the nasion-basion-opisthion angle between the normal and patient groups. All the other parameters measured in this work did not differ significantly between the two groups.

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Etude anatomo-radiologique de crânes normaux et de crânes pathologiques avec impression basilaire; utilisation de l'angle de Landzert

Résumé Cent crânes normaux ont été étudiés sur des radiographies de profil ainsi que dix crânes pathologiques présentant des impressions basilaires chez des patients traités à l'HÔpital Kenyatta de Nairobi. La plus courte distance moyenne entre le sommet de l'odontoÏde et la ligne basale de McGregor a été de 1,2±2,28 mm au-dessous de la ligne basale (extrÊmes étendues de 6 mm au-dessous à 3 mm au-dessus de la ligne basale), chez les sujets normaux et de 9±2,7 mm (6–14 mm) au-dessus de la ligne basale chez les sujets pathologiques. L'angle basai moyen était de 113±7 (102–133) chez les sujets normaux et 122±6 (113–125) chez les sujets pathologiques. L'angle moyen nasion-basion-opisthion était de 162±4 (154–169) chez les sujets normaux et 178±5 (173–185) chez les sujets pathologiques. La longueur moyenne totale du clivus était de 48±3,7 mm (43–56 mm) chez les sujets normaux et 44±6,6 (36–48 mm) chez les sujets pathologiques. Le diamètre moyen du foramen magnum était de 39±5 mm (30–48 mm), celui du foramen vertébral de l'atlas était de 21±3 mm (18 à 25 mm), celui de l'axis (18±3 mm (14–23 mm), celui de la troisième vertèbre cervicale: 16±3 mm (13–22 mm) chez les sujets normaux; chez les sujets pathologiques les chiffres étaient les suivants: foramen magnum 39±4 mm (39–45 mm), atlas 23±6 (15–30 mm), axis 19±4 mm (16–25 mm), troisième vertèbre cervicale 16±3 mm (14–20 mm). Il existe une différence significative dans la position du sommet de l'odontoÏde et la valeur de l'angle nasion-basion-opisthion entre les deux groupes. Aucun des autres paramètres mesurés dans ce travail ne présentait de différence significative entre les deux groupes.

     

Arachidonic acid inhibits hormone-stimulated cAMP accumulation in the medullary thick ascending limb of the rat kidney by a mechanism sensitive to pertussis toxin

The possible regulation of adenosine 3,5-cyclic monophosphate (cAMP) accumulation by arachidonic acid (AA) was studied in segments, microdissected from the rat kidney, which are sensitive to arginine vasopressin (AVP). In the presence of 5 M indomethacin, the addition of 5 M AA did not impair AVP-dependent cAMP accumulation (measured during 4 min at 35° C) in the cortical or outer medullary collecting tubule, but decreased this response in the thick ascending limb with an inhibition much more pronounced in the medullary portion (MTAL) than in the cortical portion. In MTAL, the response to 10 nM AVP was inhibited by 34.4±9.6% (SEM) and 65.8±5.4% with 1 M and 5 M AA, respectively, N=5 experiments. AVP-, glucagon- and calcitonin-sensitive cAMP levels in MTAL were inhibited by 5 M AA to a similar extent. AA-induced inhibition was unaffected by the presence of inhibitors of AA metabolism: (1) either 10 M indomethacin or 50 M ibuprofen added to all media; (2) a 10-min pre-incubation and a 4-min incubation of MTAL samples with 10 M eicosa-5,8,11,14-tetrayonic acid, (3) a 1-h preincubation with either 30 M SKF-525A, 20 M ketoconazole, or 20 M nordihydroguariaretic acid. In contrast to AA, 11 other saturated or unsaturated fatty acids had no inhibitory effect on the AVP-dependent cAMP level. In fura-2-loaded MTAL samples, AA induced a slow increase of the intracellular calcium concentration ([Ca²⁺]_i) which reached 21.0±3.8 nM and 92.9 ±21.4 nM over basal values (n=11) at 2 min and 4 min, respectively, after the beginning of the superfusion of 5 M AA. AA-induced inhibition of AVP-dependent cAMP accumulation was due neither to the increase in [Ca²⁺]_i elicited by AA, nor to an activation of protein kinase C because this inhibition: (1) was not blocked when MTAL samples were incubated either in zero Ca²⁺ medium, or in the presence of 1,2-bis(2-aminophenoxy)ethane-N, N, N N-tetraacetic acid (BAPTA) to chelate [Ca²⁺ _i, and (2) it was not reproduced by a pre-treatment of MTAL segments with a phorbol ester. Pre-incubation of MTAL (6 h at 35° C) with 500 ng/ml pertussis toxin (PTX) prevented AA-induced inhibition: in the presence of PTX inhibition was 24.7±6.6% vs 10 nM AVP, as compared to 81.6 ± 4.0% in control groups, i.e in the absence of PTX, N=6. AA had no effect on the cAMP level induced by 5M forskolin. It is concluded that AA inhibits AVP-dependent cAMP accumulation in the rat MTAL by a mechanism which implicates a GTP-dependent protein sensitive to PTX.     

Mechanism of inorganic phosphate diuresis secondary to saline infusions in the rat

Summary Clearance studies have been performed in rats undergoing saline diuresis. Saline infusion was increased from 0.15 to 0.5 ml/min during each experiment in order to examine the effect of extracellular fluid volume expansion on the excretion of sodium, inorganic phosphate, and calcium in normal and parathyroidectomized animals.In normal animals excretion of sodium, inorganic phosphate, and calcium increased significantly (P<0.001) from 13.7 to 56.6 Eq/min, from 0.69 to 1.34 M/min, and from 0.54 to 0.87 Eq/min, respectively, under these conditions. Fractional excretion of sodium rose from 3.8 to 13.3%, fractional excretion of inorganic phosphate from 13.8 to 27.2%, when infusion rate was elevated from 0.15 to 0.5 ml/min.In parathyroidectomized animals excretion rates of sodium and calcium were similar. In contrast, after parathyroidectomy inorganic phosphate excretion was almost abolished, being 0.0058 and 0.0121 M/min or 0.2 and 0.3% of filtered inorganic phosphate at the lower and the higher infusion rate, respectively.It is concluded, that the presence of intact parathyroids is a prerequisite for the mediation of the normal phosphaturic response secondary to saline infusions.This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft.     

High predictive value ofToxoplasma gondii IgG antibody levels in HIV-infected patients for diagnosis of cerebral toxoplasmosis

The results of serological tests forToxoplasma gondii IgG in 31 HIV-infected patients with toxoplasmic encephalitis (TE) and 49 HIV-infected patients seropositive forToxoplasma gondii but without TE were compared. All patients had a CD4+ lymphocyte count < 1 50/l. Of the TE patients, 22 (71%) were designated as having relatively high IgG levels on the basis of the followingToxoplasma IgG titre combination: Sabin-Feldman test 1256, indirect hemagglutination test 11024, direct agglutination test 114,580. Only 3 patients without TE had relatively high IgG titres. Relatively high IgG titres indicated TE with a positive predictive value of 88% in HIV-infected patients with CD4+ cell counts < 150/l, and could be observed in most patients several months prior to the first clinical and radiological signs of TE.     

Facilitation by 5-hydroxytryptamine of ATP-activated current in rat pheochromocytoma cells

The effects of 5-hydroxytryptamine (5-HT) on an inward current activated by extracellular ATP were investigated in rat pheochromocytoma PC12 cells. Under whole-cell voltage-clamp conditions 5-HT (10 M) reversibly enhanced the amplitude of the current activated by 30 M ATP. The enhancement may not be due to an increase in the number of functional channels because the current activated by 300 M ATP was not remarkably augmented compared with the current activated by 30 M ATP. The current enhancement by 100 M 5-HT was less obvious than that by 10 M 5-HT. When the current kinetics were compared, activation of the ATP-evoked current was accelerated to the same extent by either 10 or 100 M 5-HT, whereas deactivation was largely more accelerated by 100 M 5-HT. Propranolol (10 M), a 5-HT₁ receptor antagonist, or LY53857 (10 M), a 5-HT₂ receptor antagonist, exerted an agonistic effect: the ATP-activated current was facilitated by these compounds. Metoclopramide (10 M), a 5-HT₃ receptor antagonist, neither facilitated the ATP-activated current, nor blocked the current facilitation by 5-HT. Guanosine 5-O-(2-thiodiphosphate) (GDP[S]) (2 mM), the non-hydrolysable analog of guanosine 5-triphosphate (GTP), or K-252a (2 M), a protein kinase inhibitor, did not affect the facilitation by 5-HT of the ATP-activated current when they were included in the intracellular solution. The ATP-activated current pre-facilitated by 10 M dopamine was not enhanced by 10 M 5-HT. Similarly, the pre-facilitation by 5-HT attenuated the current enhancement by dopamine. The results suggest that 5-HT facilitates the ATP-activated channels through receptors that are not readily classified into conventional subclasses of 5-HT receptors. The reciprocal masking between the current facilitation by 5-HT and that by dopamine, combined with their sensitivities to the compounds involved in the intracellular solution, indicates that the facilitation by 5-HT may share not all, but some, common cellular mechanism with that by dopamine.     

Adrenaline inhibits muscarinic transmission in bullfrog sympathetic ganglia

The effect of adrenaline (Ad) on muscarinic transmission was examined in B neurones of bullfrog sympathetic ganglia by using intracellular and voltage-clamp recording methods. Bath-application of Ad (5–500 M) caused a depression of the slow excitatory postsynaptic potential (EPSP) elicited by repetitive stimulations of preganglionic nerve fibres in the presence of curare (30 M). Ad also depressed the muscarinic ACh potential induced by ionophoretic application of ACh directly to curarized sympathetic neurones in a concentration-dependent manner. Isoprenaline mimicked the effect of Ad in producing the inhibition of the muscarinic ACh potential. Propranolol antagonized the inhibitory action of Ad. Dibutyryl adenosine 3,5-monophosphate had no significant effect on the muscarinic ACh potential. Under voltage-clamp conditions, Ad caused an inward current associated with inhibition of the M-current (Brown and Adams 1980). Ad depressed the amplitude of slow postsynaptic currents produced by applications of ACh and muscarine. At a concentration of 100 M, Ad produced a 68±8% (n=12) depression of the amplitude of the muscarinic ACh current. The inhibition of muscarinic transmission induced by Ad is due to a direct suppression of the muscarinic current at the postsynaptic membrane in bullfrog sympathetic ganglia.     

Histamine H3-receptor activation inhibits acetylcholine release from the guinea pig myenteric plexus

The role of histamine H₃-receptors in the control of acetylcholine release from peripheral cholinergic neurons was evaluated in the isolated guinea pig ileum, previously loaded with³H-choline. When tested in the presence of H₁- and H₂-blockade, histamine (0.1–100 mol/l) and (R)-methylhistamine (0.01–1 mol/l) dose-dependently reduced the electrically-evoked choline outflow, with (R)-methylhistamine being a partial agonist. Selective H₃-receptor blocking drugs, thioperamide (0.1 mol/l) and impromidine (0.1 mol/l) reversed the histamine-induced inhibitory, effect. These data suggest that intestinal cholinergic nerves are endowed with histamine H₃-receptors whose activation produces an inhibitory effect upon acetylcholine release. The practical implications of these findings are obvious.     

Biophysical studies of teschen disease virus (Talfan strain)

Summary Studies have been made of the heterogeneity of infectivity and CFA in Teschen virus (Talfan strain) suspensions. Most of the infectivity was contained in two components of densities 1.46 gm./ml. and 1.35 gm./ml. The physical, chemical and immunological properties of these components have been compared. It was possible, however, to convert a large proportion of 1.46 component to 1.35 component by treating the 1.46 component with sodium dodecyl sulphate. This would indicate that the 1.46 component was a complex formed between the infective particles and cellular debris.Further studies on the growth characteristics and electron microscopy of the virus have been made.