@article{LohseKlotzDiekmannetal.1988, author = {Lohse, M. J. and Klotz, Karl-Norbert and Diekmann, E. and Friedrich, K. and Schwabe, U.}, title = {2',3'-Dideoxy-N\(^6\)-cyclohexyladenosine: an adenosine derivative with antagonist properties at adenosine receptors}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60282}, year = {1988}, abstract = {Tbe 2',3'-dideoxy analogue of the potent A\(_1\) receptor agonist, N\(^6\)-cyclohexyladenosine (CHA), was synthesized as a potential antagonist for the A\(_1\) adenosine receptor. In sturlies on adenylate cyclase 2',3'-dideoxy-N\(^6\)-cyclohexyladenosine (ddCHA) did not show agonist properties at A\(_1\) or at A\(_2\) receptors. However, it antagonized the inhibition by R-PIA of adenylate cyclase activity of fat cell membranes via A\(_1\) receptors with a K\(_i\) value of 13 \(\mu\)M. ddCHA competed for the binding of the selective A1 receptor antagonist, [\(^3\) HJ8-cyclopentyl-1,3-dipropylxantbine ([\(^3\)H]DPCPX), to rat brain membranes with a K\(_i\) value of 4.8 \(\mu\)M; GTP did not affect the competition curve. In contrast to the marked stereoselectivity of the A\(_1\) receptor for the cx- and the natural ß-anomer of adenosine, the cx-anomer of ddCHA showed a comparable affinity for the A\(_1\) receptor (K\(_i\) value 13.9 \8\mu\)M). These data indicate that the 2'- and 3'-hydroxy groups of adenosine and its derivatives are required foragonist activity at and high affinity binding to A\(_1\) adenosine receptors and for the distinction between the cx- and ß-forms.}, subject = {Toxikologie}, language = {en} } @article{LohseKlotzSchwabeetal.1988, author = {Lohse, M. J. and Klotz, Karl-Norbert and Schwabe, U. and Cristalli, G. and Vittori, S. and Grifantini, M.}, title = {2-Chloro-N\(^6\)-cyclopentyladenosine: a highly selective agonist at A\(_1\) adenosine receptors}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60279}, year = {1988}, abstract = {2-Chloro-N\(^6\)-cyclopentyladenosine (CCPA) was synthesized as a potential high affinity ligand for At adenosine receptors. Binding of [\(^3\)H]PIA to A1 receptors of rat brain membranes was inhibited by CCP A with a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent compound N\(^6\)-cyclopentyladenosine (CPA). Binding of [\(^3\)H]NECA to A\(_2\) receptors of rat striatal membranes was inhibited with a Ki-value of 3900 nM, demonstrating an almost 10,000-fold A\(_1\)-selectivity of CCPA. CCP A inhibited the activity of rat fat cell membrane adenylate cyclase, a model for the A\(_1\) receptor, with an IC\(_{50}\)-value of 33 nM, and it stimulated the adenylate cyclase activity of human platelet membranes with an EC\(_{50}\)-value of 3500 nM. The more than 100-fold A\(_1\)-selectivity compares favourably with a 38-fold selectivity of CPA. Thus, CCPA is an agonist at A\(_1\) adenosine receptors with a 4-fold higher selectivity and 2-fold higher affinity than CPA, and a considerably higher selectivity than the standard At receptor agonist R-N\(^6\) -phenylisopropyladenosine (R-PIA). CCP A represents the agonist with the highest selectivity for A\(_1\) receptors reported so far.}, subject = {Toxikologie}, language = {en} } @article{ChristlNusserHerzog1988, author = {Christl, Manfred and Nusser, R. and Herzog, C.}, title = {4-Bromoctavalen und zwei (Brommethylen)homobenzvalene anstelle eines erwarteten Bromoctabisvalens}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-58409}, year = {1988}, abstract = {No abstract available.}, subject = {Organische Chemie}, language = {de} } @article{Schartl1988, author = {Schartl, Manfred}, title = {A sex chromosomal restriction-fragment-length marker linked to melanoma-determining Tu loci in Xiphophorus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61842}, year = {1988}, abstract = {No abstract available}, subject = {Physiologische Chemie}, language = {en} } @techreport{HarthPeterFuchs1988, author = {Harth-Peter, Waltraud and Fuchs, Birgitta}, title = {A.M.I. International Study Conference: Washington D. C., 31. Juli bis 3. August 1988}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-42792}, year = {1988}, abstract = {No abstract available}, language = {de} } @article{SchmuckKobeltLinsenmair1988, author = {Schmuck, R. and Kobelt, F. and Linsenmair, Karl Eduard}, title = {Adaptations of the reed frog Hyperbolius viridiflavus (Anura, Hyperbolidae) to its arid environment: V. Iridophores and nitrogen metabolism}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78094}, year = {1988}, abstract = {Ofall amphibians living in arid habitats, reed frogs (belonging to the super species Hyperolius viridiflavus) are the most peculiar. Froglets are able to tolerate dry periods of up to 35 days or longer immediately after metamorphosis, in climatically exposed positions. They face similar problems to estivating juveniles, i.e. enduranee of long periods of high temperature and low RH with rather limited energy and water reserves. In addition, they must have had to develop meehanisms to prevent poisoning by nitrogenous wastes that rapidly accumulate during dry periods as a metabolie consequenee of maintaining a non-torpid state. During dry periods, plasma osmolarity of H. v. taeniatus froglets strongly increased, mainly through urea accumulation. Urea accumulation was also observed during metamorphic climax. During postmetamorphic growth, chromatophores develop with the density and morphology typical of the adult pigmentary pattern. The dermal iridophore layer, which is still incomplete at this time, is fully developed within 4-8 days after metamorphosis, irrespective of maintenance conditions. These iridophores mainly contain the purines guanine and hypoxanthine. The ability of these purines to reflect light provides an excellent basis for the role of iridophores in temperature regulation. In individuals experiencing dehydration stress, the initial rate of purine synthesis is doubled in eomparison to specimens continuously maintained under wet season conditions. This increase in synthesis rate leads to a rapid increase in the thiekness of the iridophore layer, thereby effectively reducing radiation absorption. Thus, the danger of overheating is diminished during periods of water shortage when evaporative cooling must be avoided. After the development of an iridophore layer of sufficient thickness for effective radiation reflectance, synthesis of iridophore pigments does not cease. Rather, this pathway is further used during the remaining dry season for solving osmotic problems eaused by accumulation of nitrogenous wastes. During prolonged water deprivation, in spite of reduced metabolic rates, purine pigments are produced at the same rate as in wet season conditions. This leads to a higher relative proportion of nitrogen end products being stored in skin pigments under dry season conditions. At the end of an experimental dry season lasting 35 days, up to 38\% of the accrued nitrogen is stored in the form of osmotically inactive purines in thc skin. Thus the osmotic problems caused by evaporative water loss and urea production are greatly reduced.}, subject = {Biologie}, language = {en} } @article{LinsenmairSchmuck1988, author = {Linsenmair, Karl Eduard and Schmuck, R.}, title = {Adaptations of the reed frog Hyperbolius viridiflavus to its arid environment. III. Aspects of nitrogen metabolism and osmuregulation in the reed frog, H. viridiflavus taeniatus, with special reference to the role of iridophores}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78108}, year = {1988}, abstract = {Reed frogs of the superspecies Hyperolius viridiflavus occur throughout the seasonally very dry and hot African savannas. Despite their small size (300-700 mg), estivating reed frogs do not avoid stressful conditions above ground by burrowing into the soil, but endure the inhospitable climate relatively unprotected, clinging to mostly dry grass sterns. They must have emcient mechanisms to enable them to survive e.g. very high temperatures, low relative hurnidities, and high solar radiation loads. Mechanisms must also have developed to prevent poisoning by the nitrogenous wastes that inevitably result from protein and nucleotide turnover. In contrast to fossorial amphibians, estivating reed frogs do not become torpid. Reduction in metabolism is therefore rather Iimited so that nitrogenous wastes accumulate faster in these frogs than in fossorial amphibians. This severely aggravates the osmotic problems caused by dehydration. During dry periods total plasma osmolarity greatly increases, mainly due to urea accumulation. Of the total urea accumulated over 42 days of experimental water deprivation, 30\% was produced during the first 7 days. In the next 7 days rise in plasma urea content was negligible. This strong initial increase of urea is seen as a byproduct of elevated amino acid catabolism following the onset of dry conditions. Tbe rise in total plasma osmolarity due to urea accumulation, however, is not totally disadvantageous, but enables fast rehydration when water is available for very short periods only. Voiding of urine and feces eeases once evaporative water loss exceeds 10\% of body weight. Tberefore, during continuous water deprivation, nitrogenous end products are not excreted. After 42 days of water deprivation, bladder fluid was substantially depleted, and urea coneentration in the remaining urine (up to 447 mM) was never greater than in plasma fluid. Feces voided at the end of the dry period after water uptake contained only small amounts of nitrogenous end products. DSF (dry season frogs) seemed not to be uricotelic. Instead, up to 35\% of the total nitrogenous wastes produced over 42 days of water deprivation were deposited in an osmotically inert and nontoxic form in iridophore crystals. The increase in skin purine content averaged 150 µg/mg dry weight. If urea had been the only nitrogenous waste product during an estivation period of 42 days, lethal limits of total osmolarity (about 700 mOsm) would have been reached 10-14 days earlier. Thus iridophores are not only involved in colour change and in reducing heat load by radiation remission, but are also important in osmoregulation during dry periods. The seIective advantages of deposition of guanine rather than uric acid are discussed.}, subject = {Biologie}, language = {en} } @article{GeiseLinsenmair1988, author = {Geise, W. and Linsenmair, Karl Eduard}, title = {Adaptations of the reed frog Hyperbolius viridiflavus to its arid environment. IV. Ecological significance of water economy with comments on thermoregulation and energy allocation}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30570}, year = {1988}, abstract = {No abstract available}, language = {en} } @article{CristalliFranchettiGrifantinietal.1988, author = {Cristalli, G. and Franchetti, P. and Grifantini, M. and Vittori, S. and Klotz, Karl-Norbert and Lohse, M. J.}, title = {Adenosine receptor agonists: Synthesis and biological evaluation of 1-deaza analogues of adenosine}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60262}, year = {1988}, abstract = {In a search for more selective A\(_1\) adenosine receptor agonists, N\(^6\)-[(R)-(-)-1-methyl-2-phenethyl]-1-deazaadenosine (1-deaza-R-PIA, 3a), N\(^6\)-cyclopentyl-1-deazaadenosine (1-deazaCPA, 3b), N\(^6\)-cyclohexyl-l-deazaadenosine (1-deazaCHA, Sc), and the corresponding 2-chloro derivatives 2a-c were synthesized from 5,7-dichloro-3-ß-D-ribofuranosyl-3Himidazo[ 4,5-b]pyridine (1). On the other band, N-ethyl-1'-deoxy-1'-(1-deaza-6-amino-9H-purin-9-yl)-ß-D-ribofuranuronamide (1-deazaNECA, 10) was prepared from 7-nitro-3-ß-D-ribofuranosyl-3H-imidazo[4,5-b]pyridine (4), in an attempt to find a more selective A\(_2\) agonist. The activity of all deaza analogues at adenosine receptors has been determined in adenylate cyclase andin radioligand binding studies. 1-DeazaNECA (10) proved tobe a nonselective agonist at both subtypes of the adenosine receptor. It is about 10-fold less active than NECA but clearly more active than the parent compound 1-deazaadenosine as an inhibitor of platelet aggregation and as a stimulator of cyclic AMP accumulation. The N\(^6\)-substituted 1-deazaadenosines largely retain the A\(_1\) agonist activity of their parent compounds, but lose some of their A\(_2\) agonist activity. This results in A\(_1\)-selective compounds, of which N\(^6\)cyclopentyl- 2-chloro-1-deazaadenosine (1-deaza-2-Cl-CPA, 2b) was identified as the most selective agonist at A\(_1\) adenosine receptors so far known. The activity of all 1-deaza analogues confirms that the presence of the nitrogen atom at position 1 of the purine ring is not critical for A\(_1\) receptor mediated adenosine actions.}, subject = {Toxikologie}, language = {en} } @article{LohseKlotzSalzeretal.1988, author = {Lohse, Martin J. and Klotz, Karl-Norbert and Salzer, Manfred J. and Schwabe, Ulrich}, title = {Adenosine regulates the \(Ca^{2+} \) sensitivity of mast cell mediator release : (histamine secretion/inositol phosphates/calcium)}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {85}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127883}, pages = {8875-8879}, year = {1988}, abstract = {Mast cells release histamine and other mediators of allergy in response to stimulation of their IgE receptors. This release is generally thought to be mediated by an elevation of cytosolic \(Ca^{2+}\). Recent evidence suggests that there might be factors that modulate the coupling between \(Ca^{2+}\) levels and mediator release. The present report identifies adenosine as one such modulator. Adenosine and several of its metabolically stable analogues were shown to enhance histamine release from rat peritoneal mast cells in response to stimuli such as concanavalin A. Metabolizing endogenous adenosine with adenosine deaminase dampened the response to stimuli, whereas trapping endogenous adenosine inside mast cells with nucleoside-transport inhibitors markedly enhanced stimulated histamine release. The metabolically stable adenosine analogue 5' -(N-ethylcarboxamido)adenosine (NECA) did not affect the initial steps in the sequence from IgE-receptor activation to mediator release, which are generation of inositol trisphosphate and increase of cytosolic \(Ca^{2+}\). However, NECA did enhance the release induced in ATP-permeabilized cells by exogenous \(Ca^{2+}\), but it had no effect on the release induced by phorbol esters. These data suggest that adenosine sensitizes mediator release by a mechanism regulating stimulus-secretion coupling at a step distal to receptor activation and second-messenger generation.}, language = {en} }