Differential nature of cross-talk among three G-coupled receptors regulating adenylyl cyclase in rat cardiomyocytes chronically exposed to receptor agonists.
Chronic exposure of cells to cognate agonists has been established to cause homologous desensitization of G protein-coupled receptors. In this work, we show that exposure of adult rat cardiomyocytes to isoproterenol (ISO) for 24 h led to the desensitization of beta-adrenoceptor (beta-AR) coupled adenylyl cyclase (AC) activity, which was associated with an increased inhibition of AC by M2-muscarinic receptor (MR) agonist, carbachol (Cch), and a decreased inhibition of AC by A1-adenosine receptor (AdR) agonist, N6-phenylisopropyladenosine (R-PIA). Chronic exposure of cells to Cch caused the desensitization of M2-MR-coupled AC, decreased the inhibitory action of R-PIA on AC and increased ISO-stimulated AC, while chronic exposure to R-PIA caused the desensitization of A1-AdR-coupled AC and modestly increased ISO-stimulated AC without any significant effect on Cch inhibition of the enzyme. Thus, chronic exposure of cardiomyocytes revealed for the first time a more complex and differential nature of cross-talk among the three major G-coupled receptors in modulating AC.
Sulakhe
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Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
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Mainra
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D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018929:Cell Culture Techniques; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists; D018721:Muscarinic Agonists; D011943:Receptors, Adrenergic, beta; D011956:Receptors, Cell Surface; D011976:Receptors, Muscarinic; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; C047235:N-(1-methyl-2-phenylethyl)adenosine; D002217:Carbachol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000241:Adenosine; D007545:Isoproterenol