The effects of Bronchodilators in common clinical use were studied by examining the cyclic AMP content in the tracheas of guinea pigs, similar in tracheobronchial sensitivity to bronchial asthma patients, and rats, similar to normal subjects, after intraperitoneal injection, using a radioimmunoassay technique with [
3H]-labelled cyclic AMP.
A) The effects of agents on the cyclic AMP content in the guinea pig trachea:
1) Ten minutes after administion of 0.5mg/kg Isoproteronol, a stimulant, or 50mg/kg Aminophylline, a xanthine conductor, the cyclic AMP content increased 2-3 times, and the two agents in combination revealed an additive tendency. When 2mg/kg of Propranolol, an adrenergic blocking agent was administered, the effect of Isoproterenol was cut in half.
2) In ten minutes, 2mg/kg Histamine increased the cyclic AMP content by 260% and when Isoproterenol was administered, it did not alter the effect of the Histamine. On the other hand, the effect of Histamine wa reduced to 1/5 by 2mg/kg of the antihistamine Diphenhydramine, but not by Propranolol.
3) The cycic AMP was doubled in 10 minutes by a 1mg/kg dose of Prednisolone, glucocorticosteroid, while 5mg/kg increased the initial value 5 times. In combination with 2mg/kg Isoproterenol or 5mg/kg Aminophylline, the additive increase was significantly higer than that produced by either agent alone. However, in combination with 2mg/kg of Imidazole, a phosphodiesterase inhibitor, and 2mg/kg Propranolol, the effect of Prednisolone was decreased by 1/3-2/3.
4) Concerning the time factor, 1mg/kg Isoproterenol peaked at 10min., declining to 50% of the peak value after 60min, thereafter further declining rapidly and reaching the initial level at 240 minutes. In the case of 1mg/kg Metaproterenol, 0.5mg/kg Salbutamol, 0.5mg/kg Clorprenaline, and 0.1mg/kg Terbutaline, the peak level was attained after 10min., and no significant change was noted after 240min., declining gradually to the initial level after 360 minutes. While 0.3mg/kg Trimetoquinol peaked at the same time, it then gradually declined.
5) Timewise the effect of 50mg/kg Aminophylline was similar to that of Metaproternol, while 1mg/kg Prednisolone reached its peak at 60min., and was still significantly higher than the initial value at 360 minutes.
B) Effects of agents on the cyclic AMP content in the rat trachea:
1) 10min. administration of 1mg/kg, 1mg/kg Metaproterenol, 50mg/kg Aminophylline or 1mg/kg Prednisolone, cyclic AMP content increased by 1.5 to 2.5 times, but the increase was only 30%-50% that of the guinea pigs. The time curve of these agents was similar in pattern to that of the guinea pig experiment, but the effects did not last so long.
2) Based on the above data, we suggest that the threshold of response in the rat tracheal muscle was higher than that of the guinea pig.
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