Experimental model of anaphylaxis-induced beta-adrenergic blockade in the airways

The influence of an anaphylactic challenge on the relaxing effects of isoproterenol, prostaglandin E1 (PGE1), forskolin, and aminophylline was examined using an isolated tracheal muscle preparation from ovalbumin (OA)-sensitized guinea pigs. As compared with histamine (4 X 10(-5) M) challenge, an anaphylactic challenge with OA (5 micrograms/mL) caused a rightward shift of the concentration-response curves for isoproterenol, PGE1, and forskolin but not for aminophylline. Their 50% effective concentrations were increased by about 1.7- to 2.8-fold of the histamine challenged preparations. These results indicate that anaphylactic challenge of the sensitized guinea pig tracheal muscle diminishes relaxing effects of isoproterenol, PGE1, and forskolin but not aminophylline. Possible mechanisms of these subsensitivities may involve both impaired coupling mechanism between receptor and adenylate cyclase and decreased adenylate cyclase activity, rather than their receptor numbers or affinity.