Shift from alpha- to beta-type adrenergic receptor-mediated responses in chronically endotoxemic rats.
Hepatocytes from chronically endotoxemic rats, or appropriate saline controls, were maintained in primary culture for 3 or 20 h. The ability of a variety of hormones to stimulate glycogen phosphorylase a was examined. At 3 h in culture, hepatocytes from endotoxemic rats had lower basal activities and exhibited impaired response to vasopressin, angiotensin II, and, to a lesser extent, norepinephrine and glucagon. The norepinephrine response was predominantly of the alpha-type in the saline rats but mixed alpha- and beta-type in the endotoxic cells. After 20 h in culture, vasopressin and angiotensin II responses were still impaired, while norepinephrine and glucagon responses were similar to those seen in the saline cells. The response to norepinephrine was predominantly of the beta-type in the endotoxic cells but still of the alpha-type in the saline cells. The results show that multiple mechanisms are involved in endotoxin-mediated inhibition of glycogen phosphorylase a activity and that alterations in intracellular calcium homeostasis play more of a significant role than adenosine 3',5'-cyclic monophosphate-mediated processes in diminished responsiveness of the liver seen in endotoxemia.
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393.
R A
RA
Pittner
J A
JA
Spitzer
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005934:Glucagon / Q000494:pharmacology; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010762:Phosphorylase a / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D012772:Shock, Septic / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology
D002712:Chlorides; D004731:Endotoxins; D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014667:Vasopressins; D000804:Angiotensin II; D005934:Glucagon; D008094:Lithium; D011433:Propranolol; D010762:Phosphorylase a; D018021:Lithium Chloride; D009638:Norepinephrine; D011224:Prazosin