Hepatocyte homologous beta 2-adrenergic desensitization is associated with a decrease in number of plasma membrane beta 2-adrenoceptors.
Preincubation of rat hepatocytes with isoproterenol induces homologous beta-adrenergic desensitization evidenced both in whole cells (cyclic AMP accumulation) and membranes (adenylyl cyclase activity). This desensitization is associated with and quantitatively similar to a loss of beta 2-adrenoceptors from the plasma membrane. Desensitization did not alter the affinities of isoproterenol for the [125I]iodocyanopindolol binding sites nor reduce the ability of guanine nucleotides to modulate agonist affinity, i.e., the receptors that remain in the surface of plasma membrane after desensitization (approximately 50%) retain their functional integrity. When membranes from isoproterenol-desensitized hepatocytes were treated with alkaline phosphatase, no attenuation of the desensitization was observed. Cholera toxin-catalyzed ADP-ribosylation was not decreased but rather slightly increased in membranes from desensitized cells as compared to the controls. Our data indicate that in hepatocytes, a loss of beta 2-adrenoceptors from the plasma membrane is closely associated to the homologous desensitization induced by isoproterenol.
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F.
O
O
Medina-Martínez
J A
JA
García-Sáinz
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D007037:Hypothyroidism / Q000503:physiopathology; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D003208:Concanavalin A; D000246:Adenosine Diphosphate Ribose; D020120:Iodocyanopindolol; D002772:Cholera Toxin; D010869:Pindolol; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D000262:Adenylyl Cyclases; D007545:Isoproterenol