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Disapearance and excretion of labeled alpha-MSH in man
Abstract:
Despite the considerable evidence for the CNS actions of alpha-melanocyte-stimulating hormone (alpha-MSH) in man, little attention has been given to its half-time disappearance from plasma and urinary excretion in normal individuals. In the first experiment, a healthy man was given 15 muCi of tritiated (3H)-alpha-MSH as a rapid IV injection. A plot of the disappearance time in plasma was characteristic of a multiexponential curve, the linear components of which were resolved by the subtraction method and half-time disappearance calculated directly from the slope of the regression line. The half-time disappearance was 1 min for the first component and 25 min for the second component. After the IV adminisration of 50 muCi of 125I-alpha-MSH in the second experiment, the two components showed halftime disappearances of 1 min and 4.8 min respectively. These times were not changed by precipitation of the plasma with 10% trichloroacetic acid. Thirty-eight percent and 42% of the label appeared in the urine 4 hr after the injection of either 3H-alpha-MSH or 125I-alpha-MSH. The results suggest that the persistence of high levels of alpha-MSH in the blood after injection in man may be too short to fully explain the CNS effects of alpha-MSH.
Insights
Alpha-melanocyte-stimulating hormone (alpha-MSH) disappears rapidly from human plasma, with half-times of 1 minute and either 4.8 or 25 minutes. This rapid clearance suggests it may not fully explain observed central nervous system effects.
Area of Science:
- Neuroendocrinology
- Pharmacokinetics
Background:
- Alpha-melanocyte-stimulating hormone (alpha-MSH) is known to have central nervous system (CNS) effects in humans.
- Limited data exists on the plasma half-life and urinary excretion of alpha-MSH in normal individuals.
Purpose of the Study:
- To investigate the plasma disappearance rate and urinary excretion of alpha-MSH in humans.
- To determine if the pharmacokinetic profile of alpha-MSH supports its observed CNS effects.
Main Methods:
- Intravenous administration of radiolabeled (tritiated and iodinated) alpha-MSH to a healthy male subject.
- Analysis of plasma disappearance curves using multiexponential analysis.
- Quantification of radiolabeled alpha-MSH in urine samples collected over 4 hours post-injection.
Main Results:
- Plasma disappearance of alpha-MSH exhibited a biexponential decay with rapid initial half-times of approximately 1 minute for both components.
- The second component's half-time was 25 minutes for 3H-alpha-MSH and 4.8 minutes for 125I-alpha-MSH.
- 38-42% of the injected radiolabel was recovered in urine within 4 hours, indicating significant excretion.
Conclusions:
- Alpha-MSH is cleared rapidly from human circulation.
- The short plasma persistence of alpha-MSH may not be sufficient to account for its prolonged CNS effects.
- Further research is needed to reconcile the rapid pharmacokinetics with observed biological activity.