Abstract

Rats were injected i.v. with 3H-iso-proterenol. Approximately 75% of the administered dose was excreted in the urine over 24 hr. Rats anaesthetized with urethane were injected i.v. with 3H- iso-proterenol and their bile and urine collected. It was found that about 92% of the administered dose were excreted over a period of 8 hr, of which about 38% were excreted in the bile and 62% in the urine. By contrast, following the injection of 3H-norepinephrine only 14% of the excreted radioactivity occurred in the bile and 86% in the urine, the total excreted amount being approximately 68% of the administered dose. If the bile of rats which had received 3H- iso-proterenol i.v. was then injected into the small intestine of other rats, increasing amounts of radioactivity were detected over a period of 10 hr in their bile and urine. The injected 3H- iso-proterenol is, as other catecholamines, rapidly O-methylated. The urine contained free 3H- iso-proterenol, 3H- iso-proterenol glucuronide, free 3-methoxy- 3 H- iso-prenaline and 3-methoxy- 3H- iso-protereno] glucuronide. No deaminated metabolites could be detected. In the bile only 3-methoxy- iso-proterenol glucuronide was found. In contrast to the findings following administration of 3H-norepinephrine, where relatively large amounts are bound in tissues like heart, spleen and suprarenals, only negligible quantities of 3H- iso-proterenol were found bound in these tissues under similar conditions. Most of the activity present in the tissues 10 min after the injection of 3H- iso-proterenol was already in the O-methylaled form. It is concluded, that the delay of the urinary excretion of radioactivity following an injection of 3H-norepinephrine is caused by its binding in the tissues and slow release. On the other hand, the delay in the urinary excretion after the injection of 3H- iso-proterenol is caused by the excretion of a relatively large amount of activity in the bile, from which it is slowly reabsorbed and finally excreted.

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