Circulation, Vol 81, 185-195, Copyright © 1990 by American Heart Association
MA Takiyyuddin, JH Cervenka, PA Sullivan, MR Pandian, RJ Parmer, JA Barbosa and DT O'Connor
In cultured cells and isolated perfused organs, catecholamines are
coreleased with chromogranin A (CgA) from adrenal chromaffin cells and
sympathetic neurons. The corelease suggests that exocytosis is the
mechanism of catecholamine secretion. To investigate whether physiologic
catecholamine secretion is exocytotic in humans, we measured plasma
norepinephrine, epinephrine, and CgA responses to differentiated stimuli of
sympathoadrenal discharge. The CgA radioimmunoassay antibody recognized
authentic CgA in normal human adrenal chromaffin vesicles. Insulin-induced
hypoglycemia and caffeine ingestion, in decreasing order of potency,
selectively stimulated epinephrine release from the adrenal medulla. During
hypoglycemia, plasma levels of epinephrine and CgA rose, and peak plasma
levels of epinephrine and CgA correlated, suggesting that gradations in
epinephrine release represented gradations in exocytosis. However,
significant increments in plasma CgA were not observed after caffeine
ingestion. Furthermore, the rise of CgA levels during hypoglycemia lagged
60 minutes behind those of epinephrine. A less-pronounced temporal
dissociation between CgA and epinephrine release was also shown in isolated
chromaffin cells in vitro. Selective adrenal vein catheterization suggested
a barrier to CgA transport across the adrenal capillary wall. Short-term,
high-intensity dynamic exercise, assumption of the upright posture,
prolonged low-intensity dynamic exercise, and smoking, in decreasing order
of potency, stimulated norepinephrine release from sympathetic nerve
endings. Only the first sympathetic neuronal stimulus resulted in
significant increments in plasma CgA, increments considerably less than
those attained during adrenal medullary activation by insulin hypoglycemia.
During high-intensity exercise, peak plasma norepinephrine and CgA levels
correlated, suggesting that gradations in norepinephrine release
represented gradations in exocytosis. The human adrenal medulla was a far
more prominent tissue source of CgA than human sympathetic nerves--adrenal
medullary homogenates contained 97-fold more CgA (micrograms/g) than
sympathetic nerve homogenates. In conclusion, catecholamine secretion
during selective stimulation of either sympathetic nerves or the adrenal
medulla is, at least in part, exocytotic. Furthermore, stimulation of the
former results in comparatively modest changes in plasma CgA compared with
changes attained during stimulation of the latter. CgA appears to be
transported by a route different from that of catecholamines from adrenal
medullary chromaffin cells to the circulation in vivo.
ARTICLES
Is physiologic sympathoadrenal catecholamine release exocytotic in humans?
Department of Medicine, University of California, San Diego.
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