Modulation of porcine adipocyte beta-adrenergic receptors by a beta-adrenergic agonist.
Mammalian cells have several mechanisms to decrease the response to beta-adrenergic agonists. Agonists are metabolized or taken up by nerve endings. The beta-adrenergic receptors (betaAR) are inactivated by phosphorylation and removed from the cell membrane, and synthesis is decreased or degradation is increased. Knowledge about adipocyte betaAR desensitization is mostly from rodent adipocytes with > or = 90% beta3AR. Porcine adipocyte betaAR have functional and ligand-binding properties that are quite different from those in many other species. Furthermore, the predominant betaAR subtype in the porcine adipocyte is the beta1AR (70 to 80%). Given these species differences, it might be expected that desensitization in porcine adipocytes would not be totally concordant with the rodent-derived model. Isolated porcine adipocytes were incubated without or with a betaAR agonist, isoproterenol. The total betaAR number, measured by ligand-binding in a crude membrane fraction, tended to be lower after 6 h of incubation without isoproterenol. The addition of 10(-5) M isoproterenol during the incubation caused the betaAR number to decrease 43% compared to cells incubated without isoproterenol. The beta1AR and beta2AR transcript concentrations both decreased 45% after 6 h of incubation without isoproterenol. There was no decrease in mRNA when cells were incubated with isoproterenol. The results suggest the betaAR were desensitized by incubation with isoproterenol, perhaps by phosphorylation and removal from the membrane, but this was not accompanied by modulation of the concentration of transcripts for beta1AR or beta2AR.
Ding
S T
ST
USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030-2600, USA. sding@bcm.tmc.edu
McNeel
R L
RL
Smith
E O
EO
Mersmann
H J
HJ
D017667:Adipocytes / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D013552:Swine / Q000378:metabolism*; D014158:Transcription, Genetic
D000318:Adrenergic beta-Agonists; D011500:Protein Synthesis Inhibitors; D011943:Receptors, Adrenergic, beta; D003609:Dactinomycin; D007770:L-Lactate Dehydrogenase; D007545:Isoproterenol