Potentiation of thermoregulatory responses to isoproterenol by beta-adrenergic antagonists.
The thermoregulatory effects of isothermogenic doses of isoproterenol (Iso) and a novel beta-agonist (BRL 35135) were tested in rats at 22 degrees C and in rats trained to bar press for radiant heat at -8 degrees C. BRL 35135 produced hyperthermia at 22 degrees C and reduced operant responding for heat at -8 degrees C, whereas Iso reduced body temperature and increased operant responding. In both situations, the negative effects of Iso on thermal balance were abolished by propranolol at doses that did not inhibit heat production. In anesthetized rats, propranolol potentiated the Iso-induced rise in brown adipose tissue and colonic temperature. The potentiation was more marked with the beta 2-selective antagonist ICI 118,551, whereas treatment with the beta 1-selective antagonist atenolol resulted in a profound Iso-induced reduction in temperature. The two selective antagonists also produced divergent responses in operant behavior in Iso-treated rats at -8 degrees C. These experiments demonstrate the extent to which responses to a nonselective agonist can be manipulated using appropriately low doses of selective antagonists and indicate that the effects of Iso on thermal balance are due to its beta 2 activity.
Carlisle
H J
HJ
Department of Psychology, University of California, Santa Barbara 93106.
Stock
M J
MJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D005334:Fever / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D010627:Phenethylamines; D011412:Propanolamines; C026777:ICI 118551; D001262:Atenolol; C063157:BRL 35135; D007545:Isoproterenol