Glucagon-Like Peptide-1-Responsive Catecholamine Neurons in the Area Postrema Link Peripheral Glucagon-Like Peptide-1 with Central Autonomic Control Sites

Citations Over TimeTop 10% of 2003 papers

Abstract

Glucagon-like peptide-1 (GLP-1) released from the gut is an incretin that stimulates insulin secretion. GLP-1 is also a brain neuropeptide that has diverse central actions, including inhibition of food and water intake, gastric emptying, and stimulation of neuroendocrine responses characteristic of visceral illness. Both intravenous and intracerebroventricular administration of GLP-1 receptor (GLP-1R) agonists increase blood pressure and heart rate and induce Fos-like immunoreactivity (Fos-IR) in autonomic regulatory sites in the rat brain. The area postrema (AP) is a circumventricular organ and has been implicated in processing visceral sensory information. GLP-1Rs are densely expressed in the AP, and peripheral GLP-1R agonists induce Fos-IR in AP neurons to a greater degree than intracerebroventricular administration. Because the AP lacks a blood-brain barrier, we hypothesized that the AP is a key site for peripheral GLP-1 to activate central autonomic regulatory sites. In this study, we found that many tyrosine hydroxylase (TH)-containing neurons in the AP expressed GLP-1Rs and Fos-IR after intravenous GLP-1R agonists. Furthermore, intravenous but not intracerebroventricular GLP-1R agonists induced TH transcription in the AP in vivo. In addition, GLP-1R agonists directly activated TH transcription in an in vitro cell system. Finally, we found that GLP-1-responsive TH neurons in the AP innervate autonomic control sites, including the parabrachial nucleus, nucleus of solitary tract, and ventrolateral medulla. These findings suggest that catecholamine neurons in the AP link peripheral GLP-1 and central autonomic control sites that mediate the diverse neuroendocrine and autonomic actions of peripheral GLP-1.

Related Papers

• → Nucleus of the solitary tract, medullary reflexes, and clinical implications(2017)114 cited
• → Circumventricular organs(2011)85 cited
• → Response of neurons in the solitary tract nucleus, area postrema and lateral parabrachial nucleus to gastric load of hypertonic saline(1993)75 cited
• → Interactions of area postrema and solitary tract in the nucleus tractus solitarius(1991)41 cited
• Cellular localization of the blood-brain barrier in the brainstem: Area postrema and nucleus tractus solitarius(2008)