Long-term inhibitory effect of cAMP on beta-adrenoceptor acquisition and nonselective attenuation of adenylyl cyclase in hepatocytes.
Long-term effects of cAMP on the surface expression of beta-adrenoceptors and adenylyl cyclase activity were investigated in primary cultures of rat hepatocytes. beta-Adrenoceptor density and catecholamine-responsive adenylyl cyclase activity increased during culturing in a biphasic manner, with a plateau of 10-20 h duration occurring approximately 10 h after plating. Treatment of hepatocyte cultures with 8-bromo-cAMP during the plateau period did not affect the density of beta-adrenoceptors. In contrast, addition of 8-bromo-cAMP, 8-chlorophenylthio-cAMP, forskolin or glucagon during a period of active recruitment of surface beta-adrenoceptors resulted in a suppression of the acquisition of beta-adrenoceptors. In both experimental situations there was a partial decrease in hormone-stimulated and basal adenylyl cyclase activity. The results suggest that cAMP exerts at least two types of long-term regulation of adenylyl cyclase in hepatocytes: a suppressive effect on beta-adrenoceptor acquisition, and a partial, nonselective decrease in adenylyl cyclase activity not involving beta-adrenoceptor down-regulation.
Department of Pharmacology, Faculty of Medicine, University of Oslo, Norway.
D
D
Sandnes
F W
FW
Jacobsen
M
M
Refsnes
T
T
Christoffersen
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D013873:Thionucleotides; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D020120:Iodocyanopindolol; D005934:Glucagon; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol