TY - JOUR A1 - Reddington, M. A1 - Klotz, Karl-Norbert A1 - Lohse, M. J. A1 - Hietel, B. T1 - Radiation inactivation analysis of the A\(_1\) adenosine receptor: decrease in radiation inactivation size in the presence of guanine nucleotide N2 - Radiation inactivation analysis of the binding of the A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes yielded a radiation inactivation size of 58 kDa. In the presence of GTPyS this was reduced to 33 kDa, in good agreement with the size of the ligand-binding subunit detected after photoaffinity labelling. The data indicate that the structural association of A\(_1\) adenosine receptors with G-protein components is altered in situ in the presence of guanine nucleotides. KW - Toxikologie KW - Adenosine receptor KW - A1 KW - Radiation inactivation KW - Target size KW - G-protein KW - (Rat brain membrane) Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60318 ER - TY - JOUR A1 - Lohse, M. J. A1 - Maurer, K. A1 - Klotz, Karl-Norbert A1 - Schwabe, U. T1 - Synergistic effects of calcium-mobilizing agents and adenosine on histamine release from rat peritoneal mast cells N2 - 1 Adenosine and its metabolically stable analogue N.etbyl-carboxamidoadenosine (NECA) enhance histamine release from rat peritoneal mast cells when tbese are stimulated by calciummobilizing agents. NECA and adenosine shift the concentration-response curve of tbe calcium ionophore A23187 to lower concentrations. 2 The potencies of NECA or adenosinein enhancing A23187-induced histamine release are dependent on the Ievel of stimulated release in tbe absence of adenosine analogues. At high Ievels of release their potencies are up to 20 times higher than at low Ievels. Consequently, averaged concentration-response curves of adenosine and NECA for enhancing bistamine release are shallow. 3 The adenosine transport blocker S-(p-nitrobenzyl)-6-thioinosine (NBTI) has no effect by itself at low Ievels of stimulated histamine release, but abolishes the enhancing effect of adenosine. At high Ievels of release, however, NBTI alone enhances the release of histamine. 4 lt is concluded that adenosine and calcium reciprocally enhance the sensitivity of the secretory processes to the effects of the other agent. The Ievels of intracellular adenosine obtained by trapping adenosine inside stimulated mast cells are sufficient to enhance histamine release substantially, suggesting that this effect may play a physiological and pathophysiological role. KW - Toxikologie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60346 ER - TY - JOUR A1 - Klotz, Karl-Norbert A1 - Lohse, M. J. A1 - Schwabe, U. A1 - Cristalli, G. A1 - Vittori, S. A1 - Grifantini, M. T1 - 2-Chloro-N\(^6\)-[\(^3\)H]cyclopentyladenosine ([\(^3\)H]CCPA) - a high affinity agonist radioligand for A\(_1\) adenosine receptors N2 - The tritiated analogue of 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine derivative with subnanomolar affinity and a 10000-fold selectivity for A1 adenosine receptors, has been examined as a new agonist radioligand. [3H]CCP A was prepared with a specifi.c radioactivity of 1.58 TBqjmmol ( 43 Ci/mmol) and bound in a reversible manner to A1 receptors from rat brain membranes with a high affinity K0 -value of 0.2 nmol/1. In the presence of GTP a K0 -value of 13 nmol/1 was determined for the low affinity state for agonist binding. Competition of several adenosine receptor agonists and antagonists for [3H]CCPA binding to rat brain membranes confrrmed binding to an A1 receptor. Solubilized A1 receptors bound [3H]CCPA with similar affinity for the high affinity state. At solubilized receptors a reduced association rate was observed in the presence of MgC12, as has been shown for the agonist [ 3H]N6-phenylisopropyladenosine ([3H]PIA). [3H]CCPA was also used for detection of A1 receptors in rat cardio myocyte membranes, a tissue with a very low receptor density. A K0 -value of 0.4 nmol/1 and a Bmax-value of 16 fmol/ mg protein was determined in these membranes. In human platelet membranes no specific binding of [3H]CCPA was measured at concentrations up to 400 nmoljl, indicating that A2 receptors did not bind [3H]CCPA. Based on the subnanomolar affinity and the high selectivity for A1 receptors [ 3H]CCPA proved to be a useful agonist radioligand for characterization of A 1 adenosine receptors also in tissues with very low receptor density. KW - Toxikologie KW - Adenosine receptors KW - Radioligauds KW - agonists Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60328 ER - TY - JOUR A1 - Tawfik-Schlieper, H. A1 - Klotz, Karl-Norbert A1 - Kreye, V. A. W. A1 - Schwabe, U. T1 - Characterization of the K\(^+\)-channel-coupled adenosine receptor in guinea pig atria N2 - In the present work we studied the pharmacological profile of adenosine receptors in guinea pig atria by investigating the effect of different adenosine analogues on 86Rb + -efflux from isolated left atria and on binding of the antagonist radioligand 8-cyclopentyl-1 ,3-[\(^3\)H]dipropylxanthine ([\(^3\)H]DPCPX) to atrial membrane preparations. The rate of \8^{86}\)Rb\(^+\) -effiux was increased twofold by the maximally effective concentrations of adenosine receptor agonists. The EC50-values for 2-chloro-N\(^6\)-cyclopentyladenosine (CCPA), R-N\(^6\)-phenylisopropyladenosine (R-PIA), 5'-Nethylcarboxamidoadenosine (NECA), and S-N\(^6\)-phenylisopropyladenosine (S-PIA) were 0.10, 0.14, 0.24 and 12.9 \(\mu\)M, respectively. DPCPX shifted the R-PIA concentration-response curve to the right in a concentration-dependent manner with a K\(_B\)-value of 8.1 nM, indicating competitive antagonism. [\(^3\)H]DPCPX showed a saturable binding to atrial membranes with a Bmax·value of 227 fmol/mg protein and a K\(_D\)-value of 1.3 nM. Competition experiments showed a similar potency for the three agonists CCPA, R-PIA and NECA. S-PIA is 200 times less potent than R-PIA. Our results suggest that the K\(^+\) channel-coupled adenosine receptor in guinea pig atria is of an A\(_1\) subtype. KW - Toxikologie KW - A1 Adenosine receptors KW - K + -channels KW - Atria KW - Radioligand binding - 86Rb + -efflux Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60333 ER - TY - JOUR A1 - Meier, Friedegund A1 - Gross, Eva A1 - Klotz, Karl-Norbert A1 - Ruzicka, Thomas T1 - Leukotriene B4 receptors on neutrophils in patients with psoriasis and atopic exzema N2 - Polymorphonuclear leukocyte (PMNL) infiltration is an important characteristic in psoriatic lesions. Elevated concentrations of the chemoattractant eicosanoid leukotriene B4 (L TB4) are present in psoriatic skin. Its chemotactic activity is mediated via high affinity receptors on PMNL. The goal of our work was to ascertain whether PMNL infiltration in psoriasis can be accounted for by functional abnormalities of the circulating PMNL due to alterations in the LTB4 receptor density or affinity (or both). No significant difference was found between patients with psoriasis, healthy controls and patients with another inflammatory dermatosis (atopic eczema) with regard to the binding parameters of LTB4 receptors on PMNL. Our findings suggest that PMNL accumulation in psoriatic skin may be the result of an excess of cutaneous hemoattractant rather than the increased readiness of psoriatic PMNL to migrate towards L TB4 due to altered LTB4 receptor density or affinity. KW - Dermatologie KW - Venerologie KW - Pharmakologie KW - Pharmazie KW - LTB4 receptor KW - neutrophils KW - psoriasis KW - atopic eczema Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86265 ER - TY - CHAP A1 - Klotz, Karl-Norbert A1 - Keil, Roger A1 - Zimmer, Franz-Josef A1 - Schwabe, Ulrich T1 - Modulation of (§H) DPCPX binding to membrane-bound ans solubilized A1 adenosine receptors by guanine nucleotides N2 - No abstract available KW - Adenosinrezeptor Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86153 ER -