caa a22 4500 469079703 CHVBK 20180323132946.0 cr unu---uuuuu 170328e19920501xx s 000 0 eng 10.1007/BF00168944 doi (NATIONALLICENCE)springer-10.1007/BF00168944 Distinct pathways for β-adrenoceptor-induced up-regulation of muscarinic acetylcholine receptors and inhibitory G-protein α-subunits in chicken cardiomyocytes [Elektronische Daten] [Christopher Reithmann, Bruno Panzner, Karl Werdan] Summary: Exposure of cardiomyocytes from chicken embryos for 3 days to the β-adrenoceptor agonist, isoproterenol, lead to a down-regulation of β-adrenoceptors by about 70% and to a decrease in isoproterenol-stimulated adenylyl cyclase activity by about 40% (homologous desensitization). In addition, the isoproterenol treatment induced an increase in the level of muscarinic acetylcholine receptors by about 30% and an increase in pertussis toxin-catalyzed ADP-ribosylation of two about 40 kDa proteins, most probably α-subunits of the inhibitory G-protein (Gi), by about a factor of two (heterologous desensitization). The purpose of the present study was to characterize the role of β-adrenoceptor-dependent and -independent mechanisms in heterologous desensitization of adenylyl cyclase. Therefore, the effect of pretreatment with the β-adrenoceptor antagonist, propranolol, with the partial agonists, celiprolol and xamoterol, and with the β-adrenoceptor-independent adenylyl cyclase activators, prostaglandin E1 and forskolin, on β-adrenoceptors, muscarinic acetylcholine receptors and pertussis-toxin-catalyzed ADP-ribosylation of G-protein α-subunits was studied. Pretreatment of the cardiomyocytes for 3 days with xamoterol or celiprolol, but not with propranolol, induced a small decrease in β-adrenoceptor number and in isoproterenol-stimulated adenylyl cyclase activity by about 15-20%. Exposure to prostaglandin E1 and forskolin lead to a more pronounced decrease in β-adrenoceptor binding and in isoproterenol-mediated adenylyl cyclase stimulation by about 40-60% (heterologous desensitization). An increase in the level of muscarinic acetylcholine receptors, similar to that induced by isoproterenol exposure, was only observed after pretreatment with the partial agonists, celiprolol and xamoterol, but not after pretreatment with the β-adrenoceptor-independent agonists, prostaglandin E1 and forskolin, nor after pretreatment with propranolol. In contrast, prostaglandin E1 and forskolin exposure lead to a similar increase in pertussis toxin-catalyzed ADP-ribosylation of about 40 kDa G-proteins as isoproterenol exposure whereas treatment with propranolol, celiprolol and xamoterol had no or only a very small effect on pertussis toxin substrates. In summary, the data suggest that, similar as shown for homologous desensitization, cyclic AMP-dependent and -independent mechanisms are also involved in heterologous desensitization of adenylyl cyclase stimulation. The β-adrenoceptor-induced upregulation of muscarinic acetylcholine receptors and of the α-subunits of pertussis toxin-sensitive G-proteins, most probably of Gi, seem to be mediated via distinct pathways. Springer-Verlag, 1992 Desensitization nationallicence Adenylyl cyclase nationallicence β-Adrenoceptor nationallicence Muscarinic acetylcholine receptor nationallicence Inhibitory G-protein nationallicence Cardiomyocyte nationallicence Reithmann Christopher Medizinische Klinik I, Klinikum Grosshadern, Universität München, Marchioninistrasse 15, W-8000, München 70, Federal Republic of Germany aut Panzner Bruno Medizinische Klinik I, Klinikum Grosshadern, Universität München, Marchioninistrasse 15, W-8000, München 70, Federal Republic of Germany aut Werdan Karl Medizinische Klinik I, Klinikum Grosshadern, Universität München, Marchioninistrasse 15, W-8000, München 70, Federal Republic of Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/5(1992-05-01), 530-540 0028-1298 345:5<530 1992 345 210 https://doi.org/10.1007/BF00168944 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00168944 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Reithmann Christopher Medizinische Klinik I, Klinikum Grosshadern, Universität München, Marchioninistrasse 15, W-8000, München 70, Federal Republic of Germany aut NATIONALLICENCE 700 1- Panzner Bruno Medizinische Klinik I, Klinikum Grosshadern, Universität München, Marchioninistrasse 15, W-8000, München 70, Federal Republic of Germany aut NATIONALLICENCE 700 1- Werdan Karl Medizinische Klinik I, Klinikum Grosshadern, Universität München, Marchioninistrasse 15, W-8000, München 70, Federal Republic of Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/5(1992-05-01), 530-540 0028-1298 345:5<530 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer