Search PubMedSearch

Biomedical subjects

I Engberg

Publications and source records attributed to I Engberg.

13 recordsLinked to original sources

Excitation of substantia nigra pars compacta neurones by 5-hydroxy-tryptamine in-vitro.

Incoming serotonergic fibres are known to make direct synaptic contact with dopamine-containing neurones in the substantia nigra pars compacta (SNc). However, the effects of 5-HT (5-hydroxytryptamine) on these cells have not been thoroughly investigated. In the present study we show that application of 10-50 microM 5-HT increases the firing frequency of SNc neurones in-vitro, and produces inward rectification in a voltage region negative to -50mV. This effect is sensitive to extracellular Cs+, but not to Ba2+, and has similar properties as the intrinsic inward rectifier current, Ih. Antagonists of the 5-HT1A and 5-HT2 receptors were inefficacious. It is concluded that 5-HT excites SNc neurones via an enhancement of the conductance underlying Ih.

Animals

Adhesion-dependent activation of mucosal interleukin-6 production.

Mucosal exposure to Escherichia coli elicits an inflammatory response in the urinary tract. Interleukin-6 (IL-6) is secreted into the urine, and polymorphonuclear leukocytes (PMNLs) are recruited to the site of infection. This study analyzed the ability of mucosally administered bacterial components to activate IL-6 and PMNL responses. P, S, and type 1 fimbrial preparations with adhesins specific for Gal alpha 1-4Gal beta, NeuAc alpha 2-3Gal, and mannose, respectively, were inoculated intravesically into lipopolysaccharide (LPS)-responder (C3H/HeN) and LPS-nonresponder (C3H/HeJ) mice. The role of the fimbrial adhesin was examined by comparing P and S fimbriae with (Adh+) and without (Adh-) the receptor-binding domain. Isolated lipid A was used in parallel. The urinary IL-6 levels were elevated after challenge with Adh+ P fimbriae, but not after challenge with the Adh- P fimbriae, Adh+ or Adh- S fimbriae, or type 1 fimbriae. The activation was not a function of contaminating LPS, since it occurred in both LPS-responder and -nonresponder mice and since isolated lipid A was a poor activator of the IL-6 response. In contrast, lipid A was a potent inducer of the PMNL response. The results suggested that the IL-6 and PMNL responses were activated via different pathways; the IL-6 response was activated mainly by an adhesion-dependent interaction with the mucosa, and the PMNLs were activated mainly by lipid A. The results emphasize the active role of the mucosal barrier in the production of mediators in response to diverse bacterial stimulants.

Animals

Persistence of Escherichia coli bacteriuria is not determined by bacterial adherence.

The role of bacterial adherence in the persistence of bacteria in the human urinary tract was analyzed. Women with chronic symptomatic urinary tract infections were subjected to deliberate colonization with nonvirulent Escherichia coli, after eradication of their current infections. E. coli organisms were instilled into the bladder through a catheter. The strain used for colonization, E. coli 83972, was isolated from a patient with stable bacteriuria. It lacked expressed adherence factors and did not belong to the uropathogenic O:K:H serotypes. Strain 83972 was transformed with the pap and pil DNA sequences encoding Gal alpha 1-4Gal beta- and mannose-specific (type 1) adhesins. Patients were colonized with a mixture of the wild-type and the transformed strains. E. coli 83972 caused stable bacteriuria for greater than 30 days in 7 of 12 individuals. In contrast, the Gal alpha 1-4 Gal beta-recognizing or mannose-binding transformants were eliminated within 48 h. The consistent superiority of the wild-type strain in establishing stable bacteriuria when compared with the adhesive transformants did not appear to be due to differences in growth rates or to plasmid segregation. Rather, the transformants expressing the adhesin determinants were selectively eliminated by the host. This suggested that the acquisition of adherence factors is not sufficient to increase the fitness of E. coli for survival in the urinary tract of humans.

Adult

Effects of anti-inflammatory agents on mucosal inflammation induced by infection with gram-negative bacteria.

Gram-negative bacterial infections of the urinary tract elicit a mucosal inflammatory response. Interleukin-6 is secreted into the urine, and polymorphonuclear leukocytes (PMNL) are recruited. In the present study we examined the effect of anti-inflammatory agents on these parameters and on bacterial clearance from the kidneys. Dexamethasone reduced interleukin-6 secretion, the PMNL response, and bacterial clearance. Diclofenac abolished the urinary interleukin-6 response but reduced the PMNL response and bacterial clearance only at the highest concentrations. Indomethacin drastically decreased bacterial clearance without the corresponding effect on interleukin-6 production or the PMNL response. The results demonstrate that the inhibition of inflammation impairs bacterial clearance from the kidneys. This is, however, not a direct function of inhibited interleukin-6 production or PMNL recruitment.

Animals

Reversal potential for noradrenaline-induced hyperpolarization of spinal motoneurons.

By using two separate electrodes with tips inside a single feline motoneuron, current-voltage characteristics were studied during extracellular iontophoresis of noradrenaline. The usually observed hyperpolarization was accompanied by an increase in membrane resistance and became larger with polarizing and smaller with depolarizing currents. During large depolarizing current injections, the noradrenaline-induced potential reversed its direction, usually at a membrane potential of about -20 millivolts. These data are compatible with the concept that noradrenaline hyperpolarizes nerve cells by decreasing resting membrane conductances to sodium and potassium ions. The observation could also be explained by a nonspecific decrease in ion permeability that is associated with a hyperpolarization due to sodium pump activation.

Animals

A comparison of extracellular and intracellular recording during extracellular microiontophoresis.

A technique is described in which a central recording microelectrode can be moved independently of a concentrically arranged multibarrelled electrode prepared for microiontophoresis. Recordings were made from cat spinal motoneurones during microiontophoretic applications of excitatory amino acids and biogenic amines with the central electrode placed first extracellularly and then intracellularly. Recording were also made from one of the iontophoretic barrels. Both intra- and extracellular electrodes were used to record action potential firing, the ventral root field (VRF) evoked by antidromic ventral root stimulation and the membrane potential (EM). They were also used to record 'focal potentials' evoked by the extracellular application of drugs to nearby neurones. The firing pattern evoked by extracellular iontophoretic applications of DL-homocysteate and glutamate was not altered significantly following impalement of the cell by the recording microelectrode. Excitatory amino acids usually caused a reduction of the VRF negative wave and evoked an additional late positive wave. These VRF changes recovered at the same rate as the extracellularly recorded, negative 'focal potentials' (Flatman and Lambert, 1979). Iontophoretic applications of biogenic amines caused small increases, small decreases, or no change of the VRF negative wave. Variable responses were also seen during intracellular recording: hyperpolarization, no response and, occasionally, depolarizations were recorded. It is concluded that, during the drug action, VRF changes are difficult to interpret and are a poor index of drug-evoked changes in neuronal excitability or EM.

Amino Acids

The actions of excitatory amino acids on motoneurones in the feline spinal cord.

1. Combined recording or ionophoretic electrodes of the concentric type were used to investigate the depolarizing responses of DL-homocysteate (DLH) and L-glutamate in cat lumbar motoneurones. 2. Typically, DLH responses were slow both in onset and recovery, while glutamate responses were fast in onset and recovery and were frequently accompanied by a post-response hyperpolarization. 3. DLH responses (smaller than those necessary to evoke firing) were accompanied by a stable decrease in GM. This decrease was usually more than could be accounted for by anomalous rectification of the membrane. 4. Small glutamate responses were accompanied by either a small decrease, no change or a small increase in GM. There was a biphasic change in GM during large responses: GM decreased during the rising phase and early part of the response plateau and thereafter increased as the depolarization was maintained. It is proposed that the high conductance state during glutamate application (but not the depolarization itself) is a manifestation of glutamate uptake. 5. Firing evoked by DLH was stable during very long applications of the drug. Firing evoked by glutamate was usually of short duration, despite the maintained depolarization. 6. No reversal potential for the DLH responses could be demonstrated, but the responses decreased in size both with hyperpolarization and depolarization of the membrane. A 'null point' of the response in the negative direction was found to be approximately -95 mV. 7. DLH resonses were insensitive to changes in the internal Cl concentration. When the external K concentration was increased by K+ ionophoresis, the DLH responses became smaller. It is concluded that the DLH response is probably mediated via a decrease in K+ conductance and that the availability of this conductance channel is potential dependent. 8. Changes in the sizes of evoked potentials (e.p.s.p.s, i.p.s.p.s and a.h.p.s) with DLH and glutamate responses were investigated. The size of each of these evoked potentials was inversely related to GM during the responses; thus they all showed stable increases during DLH responses. E.p.s.p.s recorded during DLH were of longer half-width and time-to-peak than the control, but there was no change in the maximum slope (V.sec-1). When e.p.s.p.s decreased in size with glutamate the time-to-peak remained constant. 9. Acidic amino acids have been implicated as natural excitatory transmitters. The consequence of our results for the mechanism of excitatory transmission is therefore discussed.

Action Potentials