Is physiologic sympathoadrenal catecholamine release exocytotic in humans?

Abstract

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(,ug/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 resultsin 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. (Circulation 1990;81:185-195) C atecholamine release in isolated cells and by corelease of the catecholamine storage vesicle organs is exocytotic from both adrenal medcore constituents chromogranin A (CgA)2,5 and dopa-

The catecholamine release-inhibitory peptide catestatin (chromogranin A344-364) modulates myocardial function in fish

“…As first shown in the adrenal medulla, it is co-stored and co-released with catecholamines (CAs) from the secretory vesicles of the chromaffin cells (Takiyyuddin et al, 1990;Helle et al, 2007). CgA has also been detected in secretory granules of the heart.…”

Stimulus-transcription Coupling in Pheochromocytoma Cells

“…Cell Culture-Primary cultures of bovine chromaffin cells were harvested and incubated following the method described previously (7).…”

“…17). Bovine chromaffin cells (1.5 ϫ 10 6 cells/ml) were also transfected by lipofection (plasmid DNA and Lipofectin ® concentrations both 5 g/ml) while in suspension just after harvest by collagenase digestion (7), then plated at 1 ml/well (in 6-well plates) and changed to serum-containing medium the next morning. On the third morning, nicotine (10 Ϫ3 M) or mock (vehicle) stimulation was begun and continued for the next 48 h.…”

Measurement of chromogranin A in porcine saliva: validation of a time-resolved immunofluorometric assay and evaluation of its application as a marker of acute stress

“…It is the major protein found at the core of catecholamine's storage vesicles of the adrenal medulla and sympathetic nerves chromaffin cells, from which it is co-released with epinephrine and norepinephrine (Takiyyuddin et al, 1990).…”