Browsing by Subject "Noradrenalin"

Now showing 1 - 2 of 2

Exzitatorische Pharmakologie der retinalen Spreading Depression
(2010) Sieber, Michaela; Hanke, Wolfgang
The phenomenon of Spreading Depression (SD) is a suppression of neuronal activity, propagating wave-like in the grey matter. This results from a massive ion translocation where potassium ions pour into the cell and sodium-, chlorideand calcium ions pour out of the cell. At the same time there is also a slow negative potential shift up to 30mV. Spreading Depression also occurs in the retina, a part of the central nervous system and can easily be observed there with the naked eye. This dissertation describes the effects of excitatory pharmaceuticals on neuronal tissue, using retinal spreading depression as a model system. By applying different excitatory substances, a reduction of the velocity and an inhibitory effect on the conductivity of the membranes can be observed. In the case of nicotine this may be due to the desensitization of the nicotinic AChreceptors. For caffeine, cocaine, amphetamine and metylphenidate this effect may derive from the hyperpolarisation of the tissue through open cation channels. The latency, a parameter for the excitability of the tissue, increases with the application of any of the investigated substances. This is also caused by the desensitization of the nicotinic ACh-receptors or the hyperpolarisation of the tissue, respectively. A neuroprotective effect reducing excitotoxic cell death induced by activation of NMDA-receptors was successfully verified for all substances. In the case of nicotine, the α7- and α4β2-nACh-receptors are assumed to be involved. The basic mechanism however is still unknown. A possible explanation could be the reduced excitability of the tissue through desensitization of the nACh-receptors. In the case of the remaining substances, the abidance of transmitters in the synaptic cleft suggests a neuroprotective effect through hyperpolarisation. The resulting hyperpolarisation leads to a reduced excitability of the neuronal tissue and most likely prevents over-excitation.
Stressful environments : motility and catecholamine response in Vibrio cholerae
(2014) Halang, Petra; Fritz-Steuber, Julia
The human pathogen Vibrio cholerae is able to inhabit a variety of environments. These include especially aquatic ecosystems, but the human intestine as well. V. cholerae is thus tolerant to a wide range of salinity and pH. Motility is achieved by a sodium driven polar flagellum. The affinity for Na+ to run the flagellum is determined by the stator complex PomAB, which is embedded in the cell membrane within the flagellar motor. A critical aminoacid residue for the binding of Na+ is aspartate 23 within the transmembrane helix of PomB. A mutation of this aminoacid residue leads to an immotile phenotype of V. cholerae. It was thus of interest to investigate if other polar or acidic aminoacid residues within PomB are important for the passage of Na+. Two potential candidates are serine at position 26 and aspartate at position 42 of PomB, both aminoacid residues are conserved within sodium driven flagellar stator complexes. To characterize the pathway of Na+ through the PomAB channel, the influence of chloride salts (Na+ and K+) and the pH on the motility of V. cholerae was studied. Motility decreased at elevated pH but increased if a chaotropic chloride salt was added, which excludes a direct Na+ and H+ competition in the process of binding to the conserved PomB D23 residue. Cells expressing the PomB S26A/T or D42N variants lost motility at low Na+ concentrations but regained motility in the presence of 170mM chloride. The swimming speeds of individual cells were also analyzed and revealed that S26 located within the membrane helix of PomB is required to promote very fast swimming of V. cholerae. Loss of hypermotility was observed with the S26T variant of PomB which was partially restored by lowering the pH of the external medium. Modification of PomA and PomB by N,N’-dicyclohexylcarbodiimide indicates the presence of protonated carboxyl groups in the hydrophobic regions of the two proteins. Na+ did not protect PomA and PomB from this modification. It could be demonstrated that the motility of V. cholerae is influenced by the pH and osmolality of the medium and thus, the aminoacid residues – S26 and D42 together with D23 – of PomB have a function in the passage of Na+ into the cell. The H+ rather than the Na+ concentration determines the efficiency of the motor, indicating the presence of a catalytical important hydrogen bond network in the motor channel. It is proposed that D23, S26 and D42 of PomB are part of an ion-conducting pathway formed by the PomAB stator complex. As mentioned above, V. cholerae is a pathogen which settles the human intestine. As other pathogens are able to respond specifically to the stress associated mammalian hormones epinephrine and norepinephrine it was of an interest to investigate the influence of these hormones on growth and motility of V. cholerae. The response to epinephrine and norepinephrine is mediated by the QseC sensor protein. The genome of V. cholerae comprises a gene which is homolog to qseC from E. coli. Growth and swarming of V. cholerae was enhanced in the presence of 0.1mM epinephrine or norepinephrine. qRT-PCR experiments revealed increased expression of the genes encoding the putative sensor kinase qseC and pomB, a component of the flagellar motor complex under the influence of catecholates. HPLC measurements of bacterial supernatant revealed that norepinephrine is completely degraded or metabolized after 48 h in the presence of V. cholerae, concomitant with the appearance of another, unidentified compound. On the other hand, V. cholerae seemed to stabilize epinephrine. After 48 h, 0.46% of the epinephrine added at the beginning of the growth experiment was retained. Again, a yet unidentified compound was detected. The experiments conducted in this work strongly indicate the presence of a catecholate receptor in V. cholerae.