AgRP-Expressing Adrenal Chromaffin Cells Are Involved in the Sympathetic Response to Fasting
| Autor: | Yunbing Ma, Rajesh Gupta, Manqi Wang, Matthew D. Whim |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Sympathetic Nervous System Chromaffin Cells Population Neuropeptide Antibodies Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Antibody Specificity Arcuate nucleus Internal medicine Adrenal Glands medicine Animals Agouti-Related Protein Neuropeptide Y education Research Articles education.field_of_study Adrenal gland Chemistry Receptors Melanocortin digestive oral and skin physiology Neuropeptide Y receptor 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation nervous system Hypothalamus Mutation Food Deprivation Adrenal medulla hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Homeostasis Signal Transduction |
| Zdroj: | Endocrinology. 158:2572-2584 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2016-1268 |
| Popis: | Fasting evokes a homeostatic response that maintains circulating levels of energy-rich metabolites and increases the drive to eat. Centrally, this reflex activates a small population of hypothalamic neurons that are characterized by the expression of AgRP, a neuropeptide with an extremely restricted distribution. Apart from the hypothalamus, the only other site with substantial expression is the adrenal gland, but there is disagreement about which cells synthesize AgRP. Using immunohistochemistry, flow cytometry, and reverse transcription-polymerase chain reaction, we show AgRP is present in the mouse adrenal medulla and is expressed by neuroendocrine chromaffin cells that also synthesize the catecholamines and neuropeptide Y. Short-term fasting led to an increase in adrenal AgRP expression. Because AgRP can act as an antagonist at MC3/4 receptors, we tested whether melanotan II, an MC3/4 receptor agonist, could regulate pre- and postsynaptic signaling within the adrenal medulla. Melanotan II decreased the paired-pulse ratio of evoked synaptic currents recorded in chromaffin cells; this effect was blocked by exogenous AgRP. In contrast, neither melanotan II nor AgRP altered the optogenetically evoked release of catecholamines from isolated chromaffin cells. These results are consistent with the idea that AgRP regulates the strength of the sympathetic input by modulation of presynaptic MC3/4 receptors located on preganglionic neurons. We conclude that a small population of neuroendocrine cells in the adrenal medulla, and the arcuate nucleus of the hypothalamus, express AgRP and neuropeptide Y and are functionally involved in the systemic response to fasting. |
| Databáze: | OpenAIRE |
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