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

Ayoze González-Santana,Elizabeth P Seward,Ricardo Borges,José David Machado,Judith Estévez-Herrera

doi:10.1016/j.celrep.2021.109609

Ayoze González-Santana, Elizabeth P Seward + Show 3 more

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https://doi.org/10.1016/j.celrep.2021.109609

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Journal: Cell reports	Publication Date: Aug 1, 2021
Citations: 3	License type: cc-by

Affiliation: University of Sheffield, University of La Laguna

Abstract

Agonists for glucagon-like-peptide-1 receptor (GLP-1R) are currently used for the treatment of type 2 diabetes and obesity. Their benefits have been centered on pancreas and hypothalamus, but their roles in other organ systems are not well understood. We studied the action of GLP-1R on secretions of adrenal medulla. Exendin-4, a synthetic analog of GLP-1, increases the synthesis and the release of catecholamines (CAs) by increasing cyclic AMP (cAMP) production, without apparent participation of cAMP-regulated guanine nucleotide exchange factor (Epac). Exendin-4, when incubated for 24 h, increases CA synthesis by promoting the activation of tyrosine hydroxylase. Short incubation (20min) increases the quantum size of exocytotic events by switching exocytosis from partial to full fusion. Our results give a strong support to the role of GLP-1 in the fine control of exocytosis.

Highlights

Adrenal catecholamines (CAs) actively participate in the adaptive mechanisms used to restore body homeostasis in the body, especially in response to stress conditions such as hypoglycemia, cold, hypotension or fear (Goldstein, 2010)
The glucagon-like peptide-1 (7-36)amide (GLP-1) incretin receptor is expressed in chromaffin cells The expression of glucagon-like-peptide-1 receptor (GLP-1R) mRNA in bovine chromaffin cells was verified by RT-PCR (Figure S1) and its localization determined by immunocytochemistry and confocal microscopy
Chromaffin cells were positively identified by labeling with antibodies against tyrosine hydroxylase (TH); over 95% of cells in our cultures were labeled as TH positive

Summary

Introduction

Adrenal catecholamines (CAs) actively participate in the adaptive mechanisms used to restore body homeostasis in the body, especially in response to stress conditions such as hypoglycemia, cold, hypotension or fear (Goldstein, 2010). Chromaffin cells exert their control of body functions through the secretion of stored transmitters into the blood stream using regulated exocytosis. Stored within their large dense core vesicles ( called chromaffin granules) is a cocktail of small molecules, such as adrenaline, noradrenaline, and ATP, as well as bioactive peptides, granins, and enkephalins. Because of the neural origin of chromaffin cells, the nature of their secretory products, and the basic mechanisms of regulating exocytosis, chromaffin cells have been a widely used model for the study of the molecules that control vesicle fusion (Jahn et al, 2003; Neher, 2018; Neher and Marty, 1982; Wightman et al, 1991). Because the amount of secretory products released by each quantal fusion (partial versus full fusion) and its kinetics are subject to regulation (Alvarez de Toledo et al, 2018; Shin et al., 2018), this raises the possibility that even this late stage of exocytosis may be modulated by receptors

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