Gaseous transmitter regulation of hypoxia-evoked catecholamine secretion from murine adrenal chromaffin cells

Abstract

Emerging evidence suggests that gaseous molecules, carbon monoxide (CO) and hydrogen sulfide (H2S) 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 H2S in hypoxia-induced catecholamine (CA) release from adrenal medullary chromaffin cells (AMC). Studies were performed on AMC from adult (≥6 weeks 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 [Ca2+]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 pO2 30-38 mmHg) evoked CA release and elevated [Ca2+]i. The magnitude of hypoxic response was greater in HO-2 null mice and in HO inhibitor treated WT AMC compared to controls. H2S 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 H2S donor rescued AMC responses to hypoxia in HO-2/CSE double null mice. CORM-3, a CO donor, prevented the augmented hypoxic responses in WT and HO-2 null AMC. CO donor reduced H2S 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 H2S.

Intermittent Hypoxia Increased the Expression of DBH and PNMT in Neuroblastoma Cells via MicroRNA-375-Mediated Mechanism

“…In particular, there are numerous reports concerning catecholamine synthesis in SAS patients and experimental models—more specifically, increased catecholamine secretion [ 11 , 12 ] the and up-regulation of the PNMT gene by IH [ 13 ]. Regarding catecholamine secretion from neuronal/adrenal chromaffin cells in hypoxia, hypoxia stimulates catecholamine secretion/gene expression in vitro and in vivo [ 14 , 15 , 16 ].…”

A Case for Hydrogen Sulfide Metabolism as an Oxygen Sensing Mechanism

“…CSE immunoreactivity has been identified neonatal chromaffin cells in both rats and mice and H 2 S appears to mediate hypoxic stimulation of catecholamine secretion in these animals. This likely involves HO-2/CO/CSE and BK Ca channels, similar to those described in the carotid glomus cells [ 87 , 111 , 208 ].…”

“…Carbon monoxide (CO) has been shown to inhibit CSE via protein kinase G (PKG)-dependent phosphorylation of Ser 377 on CSE, thereby inhibiting the production of H 2 S [ 110 ]. Hypoxic inhibition of hemeoxygenase-2 (HO-2) can relieve this inhibition and increase H 2 S. In this mechanism H 2 S is proposed to serve as a downstream mediator of the hypoxic response in the carotid body glomus cells, adrenal medulla, and cerebral cortical vessels [ 111 , 112 , 113 , 114 ].…”

Possible Molecular Mechanisms of Hypertension Induced by Sleep Apnea Syndrome/Intermittent Hypoxia

“…Under hypoxic conditions, the secretion of catecholamines from neuronal and adrenal chromaffin cells is increased. This increase in secretion is observed both in laboratory settings (in vitro) and in living organisms (in vivo) and is accompanied by an upregulation of gene expression related to catecholamine production [118][119][120] (Figure 2). mouse neuroblastoma cells.…”