The aim of the present study was to characterize the prejunctional modulation of evoked release of endogenous noradrenaline in rabbit vas deferens by the use of muscarinic receptor agonists and subtype-preferring antagonists. Vasa deferentia of the rabbit were stimulated electrically by trains of 120 pulses delivered at 4 Hz or trains of 30 pulses at 1 Hz. The inhibition by muscarinic agonists of the stimulation-evoked overflow of endogenous noradrenaline in the absence and presence of antagonists was used to determine affinity constants for antagonists. These values were compared with those observed at putative M1 receptors inhibiting neurogenic twitch contractions in the rabbit vas deferens and with affinity data obtained at M1(m1)-M4(m5) receptors in functional studies and binding experiments. The evoked overflow of noradrenaline from sympathetic nerves was enhanced by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) and indomethacin, indicating a tonic inhibition by endogenous A1 and P2 purinoceptor agonists and prostanoids, respectively. The stimulation-evoked overflow at 4 Hz was not sensitive to inhibition by the muscarinic agonists methacholine or 4-(4-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium iodide (4-Cl-McN-A-343). In contrast, at a stimulation frequency of 1 Hz the evoked noradrenaline release was decreased by muscarinic agonists (EC50): arecaidine propargyl ester (0.062 microM), 4-Cl-McN-A-343 (0.32 microM), 4-(4-fluorophenylcarbamoyloxy)-2-butynyl-N-methyl-pyrrolidinium tosylate (4-F-PyMcN+; 0.48 microM) and methacholine (0.86 microM). The affinity constants of most of the muscarinic antagonists [atropine: pKB = 9.47; (R)-trihexyphenidyl: pKB = 9.18; pirenzepine: pA2 = 7.68; methoctramine: pKB = 6.90] are consistent with estimates of these antagonists at M1(m1) receptors determined in various functional and binding studies. The high antagonistic potency of pirenzepine and (R)-trihexyphenidyl and the agonistic activity of 4-F-PyMcN+ argue for the involvement of M1, and against that of M2 and M3 receptors in the inhibition of evoked noradrenaline overflow. However, the high apparent pKB of 8.30 for himbacine is not in accordance with an M1 receptor; by contrast, it would be compatible with the presence of M2 or M4 receptors. The potencies of the tested muscarinic agonists and antagonists largely agree with those obtained for the inhibition of neurogenic twitch responses (0.05 Hz) in the rabbit vas deferens.(ABSTRACT TRUNCATED AT 400 WORDS)
The year 2015 marked the millennium of the first documentary evidence of the city of Leipzig as urbs Libzi. Inspired by this event the first digital elevation model (DEM 1015) from the palaeorelief at the time of the first settlement is modelled in two/three-dimensions by applying geographic information system (GIS)-technology.The article focuses on innovative multiproxy ideas to reconstruct the palaeorelief for a city centre. Thus, the topic of the project combines various scientific disciplines such as geomorphology and statistics. Qualitative data, mainly from archaeological excavations and geological drills, are linked by using GIS through surveying techniques. By applying the same method as for the DEM 1015, a recent DEM (DEM Today) is created. Furthermore, a comparison is conducted between this DEM Today and another recent DEM, which was generated with LiDAR data provided by the Staatsbetrieb Geobasisinformation und Vermessung Sachsen (GeoSN, State Operation Geobasisinformation and Surveying Saxony). A regression analysis and the descriptive comparison validate a close connection between the two recent DEMs. This supports the proposed methodology as being well suited to generate a visualization of the palaeorelief. However, models represent only a limited picture of reality. Undoubtedly, strong anthropogenic influences in the entire study area result in limiting factors which are hard to quantify. Therefore, the DEM 1015 shows the highest possible approximation of the ancient relief at the time of the first settlement. Nevertheless, the project supports further research on the landscape and settlement genesis at the study area. The DEM 1015 allows the investigation of the palaeorelief concerning geomorphological conditions during the Holocene. Furthermore, it is possible to draw inferences about how the environment has been shaped and structured by anthropogenic influences in this area over the last 1000 years. The research has the character of a case study that subsequently will open up opportunities to other areas.
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