Is physiologic sympathoadrenal catecholamine release exocytotic in humans?

Area of Science:

• Neuroendocrinology
• Cell Biology
• Physiology

Background:

• Catecholamines are coreleased with chromogranin A (CgA) from adrenal chromaffin cells and sympathetic neurons in vitro.
• This corelease suggests exocytosis as the mechanism for catecholamine secretion.

Purpose of the Study:

• To investigate if physiological catecholamine secretion in humans is exocytotic.
• To compare catecholamine and CgA responses to distinct sympathoadrenal stimuli.

Main Methods:

• Measured plasma norepinephrine, epinephrine, and CgA levels in response to various stimuli (hypoglycemia, caffeine, exercise, posture change, smoking).
• Utilized selective adrenal vein catheterization.
• Analyzed CgA content in adrenal medulla and sympathetic nerve homogenates.

Main Results:

• Insulin-induced hypoglycemia and caffeine stimulated epinephrine release from the adrenal medulla; plasma epinephrine and CgA levels correlated during hypoglycemia.
• High-intensity exercise stimulated norepinephrine release from sympathetic nerves; plasma norepinephrine and CgA levels correlated.
• The adrenal medulla was a significantly greater source of CgA than sympathetic nerves.
• CgA release from the adrenal medulla showed a temporal lag and potential transport barriers compared to catecholamines.

Conclusions:

• Catecholamine secretion from both the adrenal medulla and sympathetic nerves is, at least partly, exocytotic in humans.
• Adrenal medullary stimulation yields greater plasma CgA changes than sympathetic nerve stimulation.
• Catecholamines and CgA from adrenal chromaffin cells likely use different circulatory transport routes.