The effect of propranolol on gene expression during the blood alcohol cycle of rats fed ethanol intragastrically.
Propranolol, a beta adrenergic blocker prevents the blood alcohol (BAL) cycle in rats fed ethanol intragastrically at a constant rate by preventing the cyclic changes in the metabolic rate caused by fluctuating levels of norepinephrine released into the blood. The change in the rate of metabolism changes the rate of alcohol elimination in the blood which causes the BAL to cycle. Microarray analysis of the livers from the rats fed ethanol and propranolol showed similar changes in clusters of functionally related gene expressions. The controls and the trough of the cycle differed dramatically from the cluster pattern seen in the rats at the peaks of the blood alcohol cycle. The changes in gene expression induced by ethanol were similar when propranolol was fed without ethanol especially with the changes in the kinases and phosphatases, Toll-like receptor signaling and cytokine-cytokine receptor interaction were also changed. The changes in gene expression caused by ethanol and propranolol feeding are alike probably because both drugs induce beta adrenergic receptor desensitization.
Li
J
J
LABioMed at Harbor UCLA Medical Center, Torrance, CA 90502, USA.
Bardag-Gorce
F
F
Oliva
J
J
French
B A
BA
Dedes
J
J
French
S W
SW
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011433:Propranolol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D000319:Adrenergic beta-Antagonists; D012333:RNA, Messenger; D000431:Ethanol; D011433:Propranolol