Glucagon-like peptide-1 receptor controls exocytosis in chromaffin cells by increasing full-fusion events

Abstract

This is a repository copy of Glucagon-like peptide-1 receptor controls exocytosis in chromaffin cells by increasing full-fusion events.

Ca2+ and cAMP open differentially dilating synaptic fusion pores

“…In endocrine cells (e.g. pituitary lactotrophs, pancreatic β-cells and adrenal chromaffin cells) cAMP effects have been studied in the presence of Ca 2+ , leading to insights into regulation of Ca 2+ -evoked fusion pore behavior, electrical activity and peptide hormone release ( Calejo et al, 2013 ; 2014 ; Kucka et al, 2013 ; Guček et al, 2019 ; González-Santana et al, 2021 ). However, at the Drosophila NMJ, cAMP evokes release from DCVs in the absence of extracellular Ca 2+ and the presence of a Ca 2+ chelator without altering cytoplasmic [Ca 2+ ] ( Shakiryanova et al, 2011 ; Bulgari et al, 2018 ).…”

Cyclic Adenosine Monophosphate in Cardiac and Sympathoadrenal GLP-1 Receptor Signaling: Focus on Anti-Inflammatory Effects

“…The GLP-1R was recently shown to be present and functional also in adrenal chromaffin cells, where it modulates catecholamine (epinephrine and norepinephrine) secretion via the regulation of exocytosis ( Figure 3 ) [ 122 ]. Adrenal catecholamines are essential in the body’s response to stress [ 123 ] and, particularly, the hormone adrenaline (epinephrine) they uniquely (sympathetic neurons only release norepinephrine, the SNS neurotransmitter) secrete is vital for the generation of the classic “fight or flight” response of the body in situations of acute stress or danger [ 124 ].…”

“…Machado and colleagues reported that GLP-1R is expressed in bovine chromaffin cells and, interestingly enough, was found accumulating in the cytoplasm to a significant extent, which may suggest increased turnover of the receptor in response to the homeostatic status of the adrenal medulla (e.g., presence of stress signals, etc.) [ 122 ]. Moreover, the authors found that, although it is not a direct secretagogue of catecholamines, chromaffin cell GLP-1R enhances secretion in response to cholinergic stimulation of nicotinic cholinergic receptors (the physiological stimulus of adrenal catecholamine secretion), as well as the synthesis of catecholamines via tyrosine hydroxylase upregulation [ 122 ], the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis [ 124 ] ( Figure 3 ).…”

“…[ 122 ]. Moreover, the authors found that, although it is not a direct secretagogue of catecholamines, chromaffin cell GLP-1R enhances secretion in response to cholinergic stimulation of nicotinic cholinergic receptors (the physiological stimulus of adrenal catecholamine secretion), as well as the synthesis of catecholamines via tyrosine hydroxylase upregulation [ 122 ], the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis [ 124 ] ( Figure 3 ). GLP-1R did not appear to increase the number of secretory vesicles but rather increased the amount of catecholamine released by each individual vesicle (the so-called “quantum size”) [ 122 ].…”

“…Moreover, the authors found that, although it is not a direct secretagogue of catecholamines, chromaffin cell GLP-1R enhances secretion in response to cholinergic stimulation of nicotinic cholinergic receptors (the physiological stimulus of adrenal catecholamine secretion), as well as the synthesis of catecholamines via tyrosine hydroxylase upregulation [ 122 ], the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis [ 124 ] ( Figure 3 ). GLP-1R did not appear to increase the number of secretory vesicles but rather increased the amount of catecholamine released by each individual vesicle (the so-called “quantum size”) [ 122 ]. Finally, the authors found that this positive effect of GLP-1R on catecholamine secretion is mediated by cAMP-activated PKA and not by Epac1/2 ( Figure 3 ), and thus, differs from GLP-1R’s positive modulation of insulin secretion in pancreatic β-cells, which is mediated by both PKA and Epac [ 118 ].…”