Neural nicotinic acetylcholine responses in solitary mammalian retinal ganglion cells

Using the patch-clamp technique,whole-cell recordings from solitary rat retinal ganglion cells in culture have established the nicotinic nature of the acetylcholine responses in these central neurons. Currents produced by acetylcholine (5–20 mol/l) or nicotine (5–20 mol/l) reversed in polarity near –5 mV and were unaffected by atropine (10 mol/l). Agonist-induced currents were blocked by low doses(2–10 mol/l) of the classical ganglionic antagonists hexamethonium and mecamylamine, as well as by d-tubocurarine and dihydro--erythroidine (the latter two do not discriminate clearly between ganglionic and neuromuscular junction receptors). Treatment with the potent neuromuscular blocking agent -bungarotoxin (10 mol/l) did not affect the cholinergic responses of these cells, while toxin F (0.2 mol/l), a neural nicotinic receptor antagonist, readily abolished acetylcholine-induced currents. Thus, the experiments performed to date show that the nicotinic responses of retinal ganglion cells in the central nervous system share the pharmacology of autonomic ganglion cells in the peripheral nervous system. The ionic current carried by the nicotinic channels was selective for cations, similar to that described for nicotinic channels in other tissues. In addition, single-channel currents elicited by acetylcholine were observed in whole-cell recordings with seals > 5 G as well as in occasional outside-out patches of membrane. These acetylcholine-activated events, which had a unitary conductance of 48 pS and a reversal potential of 0 mV, represent the ion channels that mediate the neural nicotinic responses observed in these experiments on retinal ganglion cells.     

Intrinsic cholinergic excitation in the rat neostriatum: Nicotinic and muscarinic receptors

Summary An in vitro slice technique was employed to study the receptors involved in intrinsic cholinergic excitation in the rat neostriatum. The locally evoked synaptic potentials were suppressed by antinicotinic agents, mecamylamine (10 M), d-tubocurarine (3 M) or hexamethonium (100 M), but not by the antimuscarinic agent atropine (100 M). If the slices were exposed to an acetylcholinesterase (AChE)-inhibitor (paraoxon 1–20 M, physostigmine 0.1–0.5 M), the synaptic potentials were potentiated. The amplitude of the orthodromic population spike increased, and it was further facilitated when the stimulus frequencies were raised from 1–3 Hz to 10–30 Hz. The frequency facilitation following exposure to an AChE-inhibitor was blocked by atropine (1–100 M). Intracellular recording indicated that a slow depolarizing potential caused the frequency potentiation of the orthodromic discharges. Apparently rat neostriatum is similar to cholinergic systems in sympathetic ganglia and spinal Renshaw cells, in that nicotinic receptors mediate fast excitation and muscarinic receptors mediate slow excitation.     

Efficacy of the two-microelectrode voltage clamp technique in crayfish muscle

Crayfish muscle fibres of different dimensions were voltage clamped and white noise current was injected into the fibres at various distances from the voltage clamp current electrode. The clamp current was measured and power spectral densities were calculated. This method revealed the efficacy of the voltage clamp in these fibres. In large fibres (l=1.8–2.0 mm; =100–180m) a space clamp was achieved only for a band width f=40Hz. At a distance of 100m from the clamp electrodes f was 250–500Hz. In fibres of medium size (l=1.0–1.3mm; =60–120m) f was about 80Hz and about 800 Hz at a distance of 100m. In experiments with very small muscle fibres (l=400–600m; =30–50m) f was more than 500Hz. The improvement of the space clamp for the smaller muscle fibres resulted mainly from the reduced total membrane capacity,c _m, of these fibres. The limitations of the space clamp could be derived from the impedance properties of the fibres. The band width of the space clamp correlated with the band width for which the square of the absolute impedance, |Z _p|², of the muscle fibre could be described by a simple RC-model. This correlation was demonstrated in a model circuit.Power density spectra of membrane current fluctuations were measured also. To optimize the resolution of these measurements the contribution of instrumental noise was minimized. The effects of instrumental noise are discussed.This investigation was supported by the Deutsche Forschungs-gemeinschaft     

A pharmacologic study on the histamine releasing effect of atracurium and other muscle relaxants in rat isolated ileum

In this study, the effects of histamine, antihistamines (terfenadine and mepyramine), 5-hydroxytryptamine, and muscle relaxants, atracurium, vecuronium and gallamine, on the tone and contractility of rat ileum were studied and compared in vitro.The aim of the present investigation was to measure, pharmacologically, the histamine releasing effect of muscle relaxants, e.g. atracurium, vecuronium and gallamine, by comparing their contractile response in the absence and presence of antihistamines and comparing their mechanical responses with those produced by histamine and 5-hydroxytryptamine (5-HT).The results showed that the antihistamines, triludan (terfenadine) and mepyramine produced opposite effects in rat ileum. Terfenadine (0.1–20 M) produced concentration-dependent contractions in the rat ileum, whereas mepyramine (0.1–10 M) relaxed the muscle, e.g. by 1.2 g tension. Atracurium (0.5–500 M), vecuronium (0.2–200 M), and gallamine (0.1–7.0 M) produced marked contractions (1.5–4.0 g tension) in rat ileum, and these contractions were markedly reduced by mepyramine (1.3 M) or terfenadine (5 M), implicating histamine release in the generation of these contractions. However, there was some residual contraction which was not blocked by mepyramine, but by 5-HT antagonist, methysergide (1 M), indicating that a mechanism other than histamine release may be responsible for the residual contraction, i.e. release of other mediators such as 5-HT, prostaglandins, or calcium. 5-HT (0.5–500 M) and histamine (0.5–500 M) produced contractions in the rat ileum, but 5-HT was more effective than histamine in producing these contractions. Similarly, gall amine was more effective than atracurium and vecuronium in contracting the rat ileum. Since very high concentrations of muscle relaxants were used, it is suggested that in clinical concentrations, the histamine releasing effect of muscle relaxants was minimal, except that of gallamine, which may release histamine event at very low concentrations. The results are discussed in terms of pharmacologic and immunologic implications of drug reactions at the rat intestinal smooth muscle.     

On the mechanism of β-adrenergic regulation of the Ca channel in the guinea-pig heart

Dose-response relations for the increase in the amplitude of Ca current (I _Ca) on external application of isoprenaline (ISP) and internally applied cyclic AMP (cAMP) or catalytic subunit of cAMP-dependent protein kinase (C subunit) were established in single ventricular cells of the guinea pig. An intracellular dialysis technique was used. The threshold concentration was for ISP 10^–9 M, for cAMP 3 M (pipette concentration to which 10^–5 M 3-isobutyl-1-methylxanthine was added) and for C subunit around 0.4 M (pipette concentration). The concentrations for the half-maximal effect were 3.7×10^–8 M (ISP), 5.0 M (cAMP) and 0.95 M (C subunit) and for the maximum effect 10^–6 M (ISP), 15–20 M (cAMP) and 3–4 M (C subunit). For all three agents the maximum increase in the Ca current density was similar (a factor of 3–4), suggesting that they converge on the same site of the Ca channel. Accordingly, the effects of cAMP and C subunit onI _Ca were non-additive to those of ISP. From these data the relationship both between concentrations of ISP and cAMP and between those of cAMP and active C subunit in terms of their effects onI _Ca could be estimated and were compared with those obtained in broken cell preparations.A competitive inhibitor of phosphorylation, 5-adenylyl-imidodiphosphate (5 mM), greatly reduced the effects of ISP and C subunit onI _Ca. Cell dialysis with 3 mM adenosine-5-(-thio)-triphosphate, which produces a dephosphorylationresistant phosphorylation, markedly potentiated the effects of ISP and cAMP onI _Ca.The results support the hypothesis that phosphorylation of a protein within, or close to, the Ca channel by cAMP-dependent protein kinase is the mechanism of -adrenergic stimulation.This work was supported by the Deutsche Forschungsgemeinschaft, SFB 38 (membranforschung), Projekt G, and H0579/6-2     

Effects of GTPγS and fMet-Leu-Phe on rat PMN phospholipase C (PLC) activity

The PLC activities associated with the cytosol and plasma membrane subcellular fractions of rat PMN were tested for sensitivity to stimulation by GTPS and/or fMet-Leu-Phe. PMN plasma membrane PLC was stimulated 10–20% by 50 M GTPS (p<0.02). fMet-Leu-Phe alone had no effect on the plasma membrane PLC activity, but addition of fMet-Leu-Phe and GTPS together stimulated PLC activity by 20–30% (p<0.05). Neither GTPS nor fMet-Leu-Phe had any significant effect on the cytosolic PLC activity. These data demonstrate the presence of a PLC activity in rat PMN plasma membranes that is sensitive to stimulation by GTPS and fMet-Leu-Phe.     

Erythrocytenflexibilität und Strömungswiderstand in Capillaren mit einem Durchmesser unter 20 μ

Zusammenfassung Es wird eine Methode beschrieben, die es gestattet, in vitro systematische Viscositätsmessungen in Capillaren mit einem Durchmesser unter 20 auszuführen.Plangeschliffene Metallblöcke werden mit Platindraht 30 umwickelt, so daß eine Fläche aneinander liegender Drähte entsteht. Wird auf diese Fläche eine plangeschliffene Platte gepreßt, so entstehen zwischen Platte und Drähten rd. 1000 dreieckige Capillarspalten, die für Viscositätsmessungen benutzt werden können. Bei einer 30 -Wicklung hat die entstehende Capillare einen Strömungs-Querschnitt, der einer 9–10 -Capillare entspricht.Mit dieser Methode wurde der Einfluß nicht flexibler, gequollener Erythrocyten auf den Strömungswiderstand gemessen. Es konnte nachgewiesen werden, daß die Viscosität in Blöcken mit einer Wicklung von 30–50 steil ansteigt, wenn Erythrocyten um rund 20–30% quellen. In diesem Bereich wird der Fahraeus-Lindquist-Effekt aufgehoben.

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Summary A method is described by which viscosity can be measured reproducibly in capillaries with a diameter of less than 20 .Flat-ground metal blocks were wound with approximately 1000 turns of Platinum wire, diameter 30 , tightly packed in a single winding. Another flat-ground block was pressed on top of the winding so that a large number of triangular spaces occurred between the flat-ground surfaces and the wires, which could then be used for viscosity measurements. The effective diameter for bloodflow of the capillaries thus formed was 9–10 .With this method the influence of non-flexible, swollen erythrocytes on the flow resistance was investigated. The viscosity in blocks wound with wire of 30–50 is shown to rise steeply with erythrocytes which have been swollen by 20–30% of their original volume. The Fahraeus-Lindquist-effect was abolished in these capillaries.

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Mit 4 Textabbildungen     

Regulation of interleukin-1β and tumor necrosis factor secretion by the human monocytic leukemia cell line,THP-1

Activated macrophages synthesize and release the potent polypeptides, interleukin-1 (IL-1) and tumor necrosis factor (TNF). In an effort to identify the cellular signals which control cytokine production by activated macrophages, we have developed anin vitro model employing the human THP-1 cell line. In the present study, THP-1 cells primed by 1.6 M phorbol 12-myristate-13-acetate (TPA) for 4 hr demonstrated a dose-and time-dependent release of IL-1 and TNF upon activation by 20 g/ml LPS. BSA/anti-BSA-coated latex beads were also a potent stimulus for IL-1 secretion. Moreover, the combination of a suboptimal concentration of LPS (200 ng/ml) plus interferon- (0.03–333 U/ml) greatly enhanced IL-1 production. Resting THP-1 monocytes not primed by TPA did not secrete IL-1 or TNF. These distinct patterns of cytokine production may be related to the developmental stages of macrophage activation.     

Structure of bovine respiratory syncytial virus

Summary Bovine respiratory syncytial (BRS) virus propagated in calf kidney (BK) cell cultures was examined by negative contrast and thin section electron microscopy.In negative stained preparations the virus proved to be of great pleomorphism. Many particles appeared roughly spherical with an overall diamter of 80–450 m. On an average, enveloped viruses covered with spikes measured 200 m in diameter.In ultrathin sections the budding of mature virus particles from the cytoplasmic membrane was clearly visualized. The size of mature viruses was 80–130 m and that of the internal component varied from 11 to 15 m.The similarity with the ultrastructure of human respiratory syncytial (RS) virus as well as of pneumonia virus of mice (PVM) has been pointed out. It is therefore proposed to classify these three viruses together in the metamyxovirus subgroup.     

Diameter and flow velocity changes of feline small pulmonary vessels in response to sympathetic nerve stimulation

Using an X-ray television system, we measured directly changes in the internal diameter (ID), flow velocity, and volume flow of the small pulmonary vessels (100–500 m ID) in response to electrical sympathetic nerve stimulation (SNS) in anaesthetized cats before and after adrenergic receptor blockade. Flow velocity was obtained by measuring the distance that the leading edge of the contrast medium moved per 0.1 s in the small arteries. Volume flow was obtained from the product of flow velocity and cross-sectional area calculated from the ID of the small arteries. SNS was accolmplished with 10- to 15-V square-wave pulses of 2-ms duration at 20–30 Hz for 20-s periods. In response to SNS, arterial ID decreased significantly by 8–13% in the 200- to 500-m vessels but not in the 100- to 200-m vessels. In the veins, on the other hand, there was no significant ID decrease in any of the 100- to 500-m vessels. After -receptor blockade (phentolamine, 2 mg/kg i.V.), there were significant ID increases (4–9%) in the 100- to 500-m arteries in response to SNS, the maximum increases being in the 100- to 200-m arteries. After -blockade (propranolol, 2 mg/kg i.V.), the ID decrease due to SNS in the 200- to 500-m arteries was enhanced (24–27%) and, in addition, the 100- to 200-m arteries exhibited a significant ID decrease (18%). Combined and -blockade completely abolished the ID decrease due to SNS. In the veins, on the other hand, no ID change occurred even after - or -blockade. The results indicate that SNS selectively constricts 200- to 500-m arteries. The data suggests that SNS has -mediated vasoconstrictor and -mediated vasodilator effects on the 100- to 500-m arteries and that the ID response pattern to SNS depends chiefly on the balance between -mediated vasoconstriction and -mediated vasodilation. Associated with the ID decrease due to SNS, flow velocity was increased by 21%. However, SNS did not affect volume flow, because the increase in velocity was compensated by the reduction in the cross-sectional area (due to the decreased ID).     

Comparison of histamine release from peritoneal mast cells derived from diabetic and control rats

Clinical and experimental diabetes are associated with an increased number of mast cells and elevated tissue histamine concentrations. This study compared histamine release from peritoneal mast cells derived from diabetic and control rats. Experimental diabetes was induced by a single i.v. injection of streptozotocin (50 mg/kg body weight). Measurement of plasma glucose levels confimed the diabetic state. Peritoneal mast cells were stimulated for 10 min with the lectin concanavalin A (0.5–100 g/ml) in the presence or absence of phosphatidylserine, clinical dextran (0.6–1200 g/ml) in the presence of phosphatidylserine, the calcium ionophore A23187 (0.1–1 M) or the basic releasing agent compound 48/80 (0.1–10 g/ml). Histamine release induced by these agents was similar in both populations. Further studies will compare the differences in histamine release from mast cells isolated from different tissues, e.g. heart and lung. In addition, physiological stimuli which are altered in the diabetic state (e.g. hyperosmolalar solutions and free radical generating systems) are under investigation.     

Expression of surface membrane IgG on pokeweed mitogen-reactive anti-tetanus toxoid antibody-producing cells

Anti-tetanus toxoid antibody-producing cells, differentially expressing surface membrane IgM, were analyzed for the additional expression of surface membrane IgG. ⁺ and ^– cells were rosetted with anti--ox red blood cells and separated by density centrifugation into fractions enriched or depleted or ⁺ cells. These B-cell subsets were assayed for the production of IgM and IgG anti-tetanus toxoid antibody and total IgM and IgG. The results indicated that the majority of anti-tetanus toxoid antibody synthesis in the ^– fraction was by ⁺ cells. In the ⁺ fraction, however, both IgM and IgG anti-tetanus toxoid antibody production was detected in the ^+– and ⁺⁺ fraction. The inclusion of isotype-specific antisera during the first 2 days of culture further established that was expressed on the surface of the majority of the precursors for IgG anti-tetanus antibody productionin vitro. Studies performed to determine the culture requirements of ^– and ⁺ cells revealed that production of IgG anti-tetanus toxoid antibody by both cell subsets was dependent on T cells and pokeweed mitogen. However, some ^– cells could produce IgG in the presence of T cells alone.     

Electrophysiological characterization of histamine receptor subtypes in sheep cardiac Purkinje fibers

The histamine-receptor-subtype-mediated effects on action potentials of electrically driven and spontaneously active isolated sheep cardiac Purkinje fibers were investigated using H₁-and H₂-selective agonists and antagonists.In electrically stimulated Purkinje fibers, histamine (3 mol/l) increased the action potential plateau height, decreased the action potential duration measured at a repolarization level of –60 mV and enhanced the pacemaker activity. These effects were abolished by the H₂-selective antagonist cimetidine (30 mol/l), but were not impaired by the H₁-selective antagonist dimetindene (0.3 mol/l).In spontaneously active Purkinje fibers, histamine (10 mol/l) increased the spontaneous rate by 24%, the slope of diastolic depolarization by 45% and shortened the duration of the diastole by 32% of the respective control measurements. These effects were blocked by 30 mol/l cimetidine, but remained unchanged in the presence of 0.3 mol/l dimetindene.Concentration-response curves of histamine were shifted to the right by approximately 2 logarithmic units in the presence of 30 mol/l cimetidine, but were not influenced in the presence of 0.3 mol/l dimetindene. The H₂-selective agonist impromidine (0.001–0.3 mol/l) had similar actions as histamine on spontaneously active Purkinje fibers, while the H₁-selective agonist 2-(2-pyridyl-)ethylamine was ineffective. It is concluded that the pronounced stimulatory action of histamine on spontaneous activity in sheep cardiac Purkinje fibers is exclusively mediated by H₂ receptors.Dedicated to Prof. Dr. E. Mutschler on the occasion of his 60th birthday.Supported by Ministerium für Wissenschaft und Forschung, Nordrhein-Westfalen, Projekt-Nr. 40008786.     

Susceptibility to beta-lactam antibiotics in septicemia isolates from twenty-nine European laboratories

In 1984 the European Study Group on Antibiotic Resistance (ESGAR) consecutively collected gram-negative bacilli and staphylococci blood isolates and performed susceptibility testing with 11 antibiotics using the microdilution method. In all 2,578 isolates were collected: 68% gram-negative bacilli and 32% staphylococci. The MICs of ampicillin and cefazoline for the susceptible gram-negative bacilli were 1–8g/ml; of piperacillin0.5–4; of Sch 34343, cefotaxime, moxalactam, ceftazidime and aztreonam0.5–2g/ml; of cefoxitin, cefuroxime and cefamandole0.5–8g/ml. For susceptible staphylococci the MICs of cefazoline and cefuroxime were0.5–1g/ml, and of cefoxitin, moxalactam, ceftazidime and cefotaxime,0.5–32 g/ml. The resistance levels varied between laboratories and countries, being lower in Northern Europe. In clinical protocols on patients with gram-negative septicemia from whom cefazoline-resistant strains were isolated, cefotaxime was the beta-lactam most commonly used (12%). In protocols on patients with staphylococcal septicemia from whom gentamicin-resistant or cefazoline-resistant strains were isolated, the most commonly used beta-lactam was cloxacillin (6%).     

On three new species of the genus Criconemoides Taylor, 1936 (Nematoda: Criconematidae) from North India

Summary The definition of the genus Criconemoides should be extended so as to include those aberrant forms which possess slight cuticular ornamentation. Three new species of the genus Criconemoides Taylor, 1936 are described and illustrated from North India. Criconemoides aberrans n. sp. is distinctive in having 38–43 body annules, rough cuticular outgrowths on the body, 68–78 long spear, bluntly rounded tail, absence of spermatheca and males unknown. Criconemoides neoaxeste n. sp. has 45–49 body annules marked with faint longitudinal lines and rough posterior margins, 65–75 long spear, rounded tail terminus, vulva located at 7th or 8th annule from the posterior end and larva having a cuticular flap with rough margins on each annule. Criconemoides macrolobatus n. sp. is distinguished by 81–86 body annules, very large oval sublateral lobes, 71–75 long spear, tail terminus rounded and the absence of spermatheca and males unknown.

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Zusammenfassung Die Definition der Gattung Criconemoides sollte so erweitert werden, daß auch solche aberranten Formen eingeschlossen werden können, die leichte cuticulare Ornamente besitzen. Drei neue Arten der Gattung Criconemoides Taylor (1936) aus Nordindien werden beschrieben und abgebildet. C. aberrans n. sp. ist deutlich charakterisiert durch 38 bis 43 Körperringe, cuticulare Auswüchse am Körper, 68–78 langen Lanzen, stumpf-abgerundeten Schwanz; Spermatheke fehlt, Männchen nicht bekannt. C. neoaxeste n. sp. hat 45–49 Körperringe mit feiner longitudinaler Linienzeichnung und groben hinteren Rändern, 65–75 lange Lanzen, abgerundetes Schwanzende. Vulva im 7. oder 8. Ring vom hinteren Ende lokalisiert; die Larven haben eine cuticulare Klappe mit groben Rändern an jedem Ring. C. macrolobatus n. sp. ist gekennzeichnet durch 81–86 Körperringe mit sehr breitovalen sublateralen Loben, 71–75 lange Lanzen, Schwanzende abgerundet, Spermatheken fehlen und Männchen unbekannt.

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With 17 Figures in the Text     

Macromolecular structure of axon membrane and action potential conduction in myelin deficient and myelin deficient heterozygote rat optic nerves

Summary The macromolecular structure of the axon membrane in optic nerves from 25-day-old male littermate control and myelin deficient (md) rats and 16-month-old md heterozygotic rats was examined with quantitative freeze-fracture electron microscopy.The axon membrane of control optic nerves displayed an asymmetrical partitioning of intramembranous particles (IMPs); P-fracture faces of myelinated internodal axon membrane were more particulate than those of pre-myelinated axons (1600 1100 m^–2, respectively), while relatively few IMPs (150 m^–2) were present on external faces (E-faces) of internodal or pre-myelinated axon membrane. Amyelinated axons of md optic nerves also exhibited an asymmetrical partitioning of IMPs; protoplasmic membrane face (P-face) IMP densities, taken as a group, exhibited a wide range (600–2300 m^–2) and, in most regions, E-faces displayed a relatively low IMP density (175 m^–2). Axons of > 0.4 m diameter exhibited significantly greater mean P-face IMP density than axons < 0.4 m diameter. Aggregations of E-face IMPs (350 m^–2) were occasionally observed along amyelinated axon membrane from md optic nerves.Optic nerves from md heterozygote rats exhibit myelin mosaicism, permitting examination of myelinated and amyelinated axon membrane along the same tract. The axon membrane exhibits different ultrastructure in these two domains. Myelinated internodal axon membrane from md heterozygote optic nerves exhibits similar P- and E-face IMP densities to those of control internodal axolemma (1800 and 140 m^–2, respectively). Amyelinated axons in the heterozygote exhibit a membrane structure similar to amyelinated axons in md optic nerve. P-face IMP density of large diameter (> 0.4 m) amyelinated axons from md heterozygote optic nerves is significantly greater than that of small calibre (< 0.4 m) axons. In most regions, amyelinated axon membrane exhibits a relatively low E-face IMP density (200 m^–2); however, focal aggregations (400 m^–2) of E-face particles are present.Electrophysiological recordings demonstrate that amyelinated axons in md optic nerves support the conduction of action potentials. Compound action potentials in md optic nerves exhibit a monophasic configuration, even at 20-days postnatal, similar to that of pre-myelinated optic nerve of 7-day-old normal rats. Moreover, conduction velocities in the amyelinated 20-day-old md optic nerve are similar to those displayed by pre-myelinated axons from 7-day-old optic nerves. These results are consistent with persistence of action potential conduction in md axons, despite the absence of myelination in the optic nerves of the md mutant.     

Effect of lysolecithin on blood vessel reactivity and of some ethers and esters of glycerophosphocholine and phosphocholine,respectively, on aggregation of rat platelets

Infusion of lysolecithin (LPC; e.g. 88 g/ml for 0.5–1.0 min) did not significantly impair the vasopressor action of norepinephrine (NE), prostaglandin F₂ (PGF₂) and extract of posterior pituitary (EPP) in the isolated perfused hind legs of rats. In other words, vascular smooth muscle behaves differently from the smooth muscle of the guinea-pig small intestine, since, in the latter, contractions evoked by acetylcholine, prostaglandins etc., are inhibited by LPC. Triton X 100 which, by comparison, was used as a detergent effective on the guinea-pig small intestine, depressed the vasopressor effect of NE, PGF₂ and EPP.LPC, at low concentrations (40 mol/l), potentiated (15% max.) ADP-induced platelet aggregation (PA) in rat PRP but, at high concentrations, inhibited PA (IC₅₀=390 mol/l). 2-Hexadecylglycerophosphocholine and its short-chain 1-alkyl ethers, which are structurally related to platelet-activating factor, as well as some long-chain alkanol phosphocholine esters, were somewhat more active than LPC. Dipalmitoyllecithin (4–700 mol/l) was without any effect.     

Light and electron microscopic studies onMyxobolus cotti El-Matbouli and Hoffmann, 1987 infecting the central nervous system of the bullhead (Cottus gobio)

Myxobolus cotti (Myxozoa: Myxosporea) is described as found in the central nervous system of the bullhead (Cottus gobio) caught in the Alpine lake Königssee and in a brook in the Bavarian Forest, Federal Republic of Germany (El-Matbouli and Hoffmann 1987). Aggregations of spores and polysporoblastic trophozoites compressed and replaced large areas of the white and grey matter of the brain and spinal cord. These aggregations may be surrounded by a thin, connective tissue capsule; in a few cases they were associated with loose infiltrates of glial cells. Neither conspicuous tissue reactions nor inflammatory responses were evident. No other organs were seen to be infected withM. cotti. Mature spores are oval, with a tapering anterior end, and the pyriform polar capsules are nearly equal in size. Fresh spores measured 8.9–15.1 m in length (mean, 12.4 m) and 8–12.4 m in width (mean, 9.6 m); polar capsules were 4.3–9 m long (mean, 6.4 m); and 2–3.8 m wide (mean, 2.9 m). Light microscopy, the ultrastructure of pansporoblasts, sporogenesis and mature spores are described.     

Histamine-induced microvascular permeability increases in hamster skin: a response predominantly mediated by H2-receptors

The pharmacology of histamine-induced increases in cutaneous microvascular permeability was investigated in the hamster by (a) examining the effects of cimetidine and pyrilamine on the increase in microvascular permeability evoked by graded doses of intradermally-injected histamine, and (b) comparing the cutaneous microvascular permeability responses to graded doses of impromidine (0.1–100 g), dimaprit (1–100 g) and -histine (0.1–100 g). Pretreatment with pyrilamine (0.1 mg/kg i.v. bolus injection) did not reduce the increase in microvascular permeability produced by any dose of histamine. In contrast, cimetidine (0.5 mg/kg/min i.v. infusion) significantly inhibited the microvascular permeability responses to 10 and 100 g histamine. Although neither cimetidine nor pyrilamine significantly altered the microvascular permeability response to 0.1 and 1g histamine, inhibition was afforded by a cimetidine-pyrilamine combination. These results suggest a predominantly H₂-receptor mediated phenomenon with a minor H₁-receptor mediated component. Studies with the H₂-receptor agonists impromidine and dimaprit and the H₁-receptor agonist -histine provide further support for this contention. Dimaprit and impromidine caused a dose-dependent increase in cutaneous microvascular permeability, but betahistine produced only a relatively modest response. In other laboratory species, increased cutaneous microvascular permeability appears to be mediated solely by H₁-receptors. Therefore, the hamster skin appears unique with respect to the pronounced H₂-receptor involvement in histamine-induced microvascular permeability changes.     

Basolateral membrane conductance in A6 cells: effect of high sodium transport rate

Conductance of apical and basolateral membranes in short-circuited cultured renal distal cells (A6) was determined using microelectrodes. Epithelia were pre-incubated with 0.1 mol/l dexamethasone in the presence of 4 mol/l amiloride to prevent increase in apical Na⁺ entry. Omission of amiloride increased the I _SC from 5.7 to 27.6 A/cm² due to the rise in apical membrane conductance from 21 to 595 S/cm². Apical fractional resistance decreased from 0.89 to 0.40 and cells depolarized from –52 to –4 mV. Basolateral membrane conductance, which was 320 S/cm² at partially inhibited transport, was not significantly altered during the first 2 min following establishment of high transport activity; it started to increase thereafter reaching a more than threefold higher value of 1324 S/cm² within 12 min. The gain cannot be explained by increase in partial K⁺ conductance. Disappearance of the conductance after reduction of basolateral Cl^– or in the presence of the Cl^– channel blocker 5-nitro-2-(3-phenylpropylamino)benzoate indicates a Cl^– conductance, which appears to be activated by depolarization.