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Inactivation of monoamines by the lung
Abstract:
Inactivation of monoamines was the first pharmacokinetic property of lung to be identified. For some amines inactivation in perfused lung but not in liver is limited by uptake. Inactivation of beta-phenylethylamine in lung is limited not by uptake but by the activity of intracellular monoamine oxidase. The uptake of this amine is like that of basic drugs such as amphetamine and propranolol. Changes in the external environment of the lung (exposure in vivo to gaseous anaesthetics or to high concentrations of oxygen, greater than 95%) change amine inactivation processes in lung. The oestrous cycle and administration of ovarian steroids also affect the inactivation of 5-hydroxytryptamine and phenylethylamine. Monoamine oxidase activity in lung homogenates is highest at met- and lowest at pro-oestrus for both substrates. However, in perfused lung, inactivation is better correlated with variations in uptake. Therefore the main effect of the oestrous cycle is on uptake rather than on enzymic activity. Uptake processes are thus crucial determinants of monoamine activation in lung and the pharmacokinetic properties of lung are capable of responding to changes in its internal or external environment.
Insights
Lung inactivation of monoamines, like beta-phenylethylamine, depends on uptake and monoamine oxidase (MAO) activity. Environmental and hormonal changes significantly impact these lung pharmacokinetic processes.
Area of Science:
- Pharmacology
- Pulmonary Physiology
- Biochemistry
Background:
- The lung's capacity to inactivate monoamines was an early pharmacokinetic discovery.
- While liver monoamine inactivation is often uptake-limited, lung inactivation can be limited by intracellular enzymes like monoamine oxidase (MAO).
Purpose of the Study:
- To investigate the determinants of beta-phenylethylamine inactivation in the lung.
- To explore how external lung environment and hormonal fluctuations affect monoamine inactivation in lung tissue.
Main Methods:
- Studied beta-phenylethylamine uptake and inactivation in perfused lung models.
- Assessed monoamine oxidase activity in lung homogenates.
- Examined effects of gaseous anesthetics, high oxygen concentrations, and the oestrous cycle on lung amine metabolism.
Main Results:
- Lung inactivation of beta-phenylethylamine is primarily limited by monoamine oxidase (MAO) activity, not uptake.
- Exposure to anesthetics or high oxygen levels alters lung amine inactivation.
- The oestrous cycle and ovarian steroids influence the inactivation of 5-hydroxytryptamine and phenylethylamine.
- While MAO activity varies cyclically, lung inactivation correlates better with uptake variations, suggesting hormonal effects predominantly impact uptake.
Conclusions:
- Uptake processes are critical determinants of lung monoamine inactivation.
- Lung pharmacokinetic properties are adaptable and responsive to internal and external environmental shifts.