Supersensitivity to catecholamines after inhibition of extraneuronal uptake (uptake2) or O-methylation.

The influence of inhibition of uptake2 and of O-methylation on beta-adrenoceptor-mediated responses of guinea-pig trachea and rat uterus to some catecholamines was compared. The responses were more markedly enhanced by inhibition of O-methylation (by U-0521) than by inhibition of uptake2 (by hydrocortisone). The ranking order for the degree of super-sensitivity caused by either U-0521 or hydrocortisone was different in the two tissues, suggesting differences between the O-methylating systems of those tissues. In experiments with 3H-isoprenaline metabolism, hydrocortisone had a weak inhibitory effect on O-methylation in both tissues.