Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling
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- It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxyphenytisopropyladenosine [(R)-AHPIA] into the A, adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of celular cAMP Ieveis [Mol. Pharmacol. 30:403-409 (1986)]. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenytate cyclase Stimulation via these receptors. ThisIt has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxyphenytisopropyladenosine [(R)-AHPIA] into the A, adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of celular cAMP Ieveis [Mol. Pharmacol. 30:403-409 (1986)]. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenytate cyclase Stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies in-dicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase Stimulation of up to SOOk of the control value. Similarly, the activation via these 10-20% of receptors occurs with a halflife that is only 2 times Ionger than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenytate cyclase Stimulation. These observations require a modification of the models of receptor-adenytate cyclase coupling, which is described in the accompanying paper [Mol. Pharmacol. 39:524-530 (1991)].…
Autor(en): | Martin J. Lohse, Karl-Norbert Klotz, Ulrich Schwabe |
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URN: | urn:nbn:de:bvb:20-opus-86073 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Pharmakologie und Toxikologie |
Sprache der Veröffentlichung: | Englisch |
Erscheinungsjahr: | 1991 |
Originalveröffentlichung / Quelle: | In: Molecular Pharmacology, 1991, 39, S.517-523 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Normierte Schlagworte (GND): | Adenosinrezeptor |
Datum der Freischaltung: | 03.06.2014 |
Lizenz (Deutsch): | Deutsches Urheberrecht |