Open AccessGaseous transmitter regulation of hypoxia-evoked catecholamine secretion from murine adrenal chromaffin cells
Author(s) -
Anna Gridina,
Xiaoyu Su,
Shakil A. Khan,
Yingjie Peng,
Benjamin Wang,
Jayasri Nanduri,
Aaron P. Fox,
Nanduri R. Prabhakar
Publication year - 2021
Publication title -
journal of neurophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.302
H-Index - 245
eISSN - 1522-1598
pISSN - 0022-3077
DOI - 10.1152/jn.00669.2020
Subject(s) - catecholamine , hypoxia (environmental) , secretion , adrenal medulla , chromaffin cell , endocrinology , medicine , neuroscience , chemistry , biology , oxygen , organic chemistry
Emerging evidence suggests that gaseous molecules, carbon monoxide (CO), and hydrogen sulfide (H 2 S) generated by heme oxygenase (HO)-2 and cystathionine γ-lyase (CSE), respectively, function as transmitters in the nervous system. Present study examined the roles of CO and H 2 S in hypoxia-induced catecholamine (CA) release from adrenal medullary chromaffin cells (AMCs). Studies were performed on AMCs from adult (≥6 wk of age) wild-type (WT), HO-2 null, CSE null, and HO-2/CSE double null mice of either gender. CA secretion was determined by carbon fiber amperometry and [Ca 2+ ] i by microflurometry using Fura-2. HO-2- and CSE immunoreactivities were seen in WT AMC, which were absent in HO-2 and CSE null mice. Hypoxia (medium Po 2 30-38 mmHg) evoked CA release and elevated [Ca 2+ ] i . The magnitude of hypoxic response was greater in HO-2 null mice and in HO inhibitor-treated WT AMC compared with controls. H 2 S levels were elevated in HO-2 null AMC. Either pharmacological inhibition or genetic deletion of CSE prevented the augmented hypoxic responses of HO-2 null AMC and H 2 S donor rescued AMC responses to hypoxia in HO-2/CSE double null mice. CORM3, a CO donor, prevented the augmented hypoxic responses in WT and HO-2 null AMC. CO donor reduced H 2 S levels in WT AMC. The effects of CO donor were blocked by either ODQ or 8pCT, inhibitors of soluble guanylyl cyclase (SGC) or protein kinase G, respectively. These results suggest that HO-2-derived CO inhibits hypoxia-evoked CA secretion from adult murine AMC involving soluble guanylyl cyclase (SGC)-protein kinase G (PKG)-dependent regulation of CSE-derived H 2 S. NEW & NOTEWORTHY Catecholamine secretion from adrenal chromaffin cells is an important physiological mechanism for maintaining homeostasis during hypoxia. Here, we delineate carbon monoxide (CO)-sensitive hydrogen sulfide (H 2 S) signaling as an important mediator of hypoxia-induced catecholamine secretion from murine adrenal chromaffin cells. Heme oxygenase-2 derived CO is a physiological inhibitor of catcholamince secretion by hypoxia and the effects of CO involve inhibition of cystathionine γ-lyase-derived H 2 S production through soluble guanylyl cyclase-protein kinase G signaling cascade.