How does the stimulus define exocytosis in adrenal chromaffin cells?

Abstract

The extent and type of hormones and active peptides secreted by the chromaffin cells of the adrenal medulla have to be adjusted to physiological requirements. The chromaffin cell secretory activity is controlled by the splanchnic nerve firing frequency, which goes from approximately 0.5 Hz in basal conditions to more than 15 Hz in stress. Thus, these neuroendocrine cells maintain a tonic release of catecholamines under resting conditions, massively discharge intravesicular transmitters in response to stress, or adequately respond to moderate stimuli. In order to adjust the secretory response to the stimulus, the adrenal chromaffin cells have an appropriate organization of Ca channels, secretory granules pools, and sets of proteins dedicated to selectively control different steps of the secretion process, such as the traffic, docking, priming and fusion of the chromaffin granules. Among the molecules implicated in such events are the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, Ca sensors like Munc13 and synaptotagmin-1, chaperon proteins such as Munc18, and the actomyosin complex. In the present review, we discuss how these different actors contribute to the extent and maintenance of the stimulus-dependent exocytosis in the adrenal chromaffin cells.

Intricacies of the Molecular Machinery of Catecholamine Biosynthesis and Secretion by Chromaffin Cells of the Normal Adrenal Medulla and in Pheochromocytoma and Paraganglioma

“…In recent years, considerable progress has been made in unravelling the complex molecular background and the functional elements of the highly regulated exocytotic machinery in adrenomedullary chromaffin cells (Figure 2) [145,171,172]. Release of acetylcholine by the splanchnic nerve activates the nicotinic receptor on chromaffin cells, resulting in opening of the ionophoric part of the receptor protein, thereby allowing the entry of extracellular sodium (Na + ) and calcium (Ca 2+ ).…”

“…The distribution of the different calcium channel subtypes is species specific. The P/Q-type calcium channel predominates in human adrenomedullary chromaffin cells [167,171,172]. As a consequence of elevated intracellular Ca 2+ concentrations, the exocytotic machinery and the regulatory components for vesicular exocytosis are activated, which occurs through a pathway consisting of secretory vesicle recruitment, docking, priming, and fusion with the plasma membrane.…”

Hypoxia pathway proteins regulate the synthesis and release of epinephrine in the mouse adrenal gland

“…Under basal conditions, exocytosis from the chromaffin cells is a strictly controlled process that largely depends on calcium uptake [50][51][52][53]. However, it can be further enhanced by additional stimuli, including hypoglycaemia, hypotension, hypoxemia and emotional distress [4,17,53,54]. Interestingly, it has been recently reported that EPO Tg6 mice are strongly hypoglycaemic and that low BGL correlates with the degree of erythropoiesis [22,55].…”

The Ca2+ channel subunit CaVβ2a‐subunit down‐regulates voltage‐activated ion current densities by disrupting actin‐dependent traffic in chromaffin cells

“…Chromaffin cells from the adrenal medulla are electrically excitable cells that release catecholamines and neuropeptides in response to stress. They are equipped with a set of ion channels that control membrane excitability, Ca 2+ influx signals, and consequently the secretory response (Marengo and Cárdenas, ). Since these neuroendocrine cells need to respond to a wide range of physiological situations, from maintaining a tonic release under basal conditions to a massive release of transmitters in response to stress, a tight regulation of the membrane excitability and Ca 2+ signals is required.…”

“…Chromaffin cells from the adrenal medulla are electrically excitable cells that release catecholamines and neuropeptides in response to stress. They are equipped with a set of ion channels that control membrane excitability, Ca 2+ influx signals, and consequently the secretory response (Marengo and C ardenas, 2018). Since these neuroendocrine cells need Fig.…”