Effects of the gasotransmitter H2S on pulmonary ion transport processes

• Applicant: Professor Dr. Mike Althaus
• Subject Area: Animal Physiology and Biochemistry
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 198451743

The transport of ions across pulmonary epithelia is a crucial mechanism for the regulation of a thin liquid layer which covers these epithelia. Deregulations in ion transport processes can lead to the accumulation of fluid in the distal lung (oedema) or an increased viscosity of the liquid and, consequently, mucus plugging of the airways (cystic fibrosis). A precise regulation of transepithelial ion transport and involved ion channels/transporters is therefore essential for lung physiology. A potential new regulator of pulmonary ion transport is the gasotransmitter hydrogen sulfide (H2S). H2S can be enzymatically produced in lung epithelial cells and causes, amongst other things, a reduction of the transepithelial absorption of sodium. However, physiologically/patho-physiologically relevant stimuli of endogenous H2S synthesis remain unknown. Such potential stimuli are planned to be identified and characterized in this project. Aside from the absorption of sodium, a secretion of chloride across pulmonary epithelia is important. The balance between sodium absorption and chloride secretion drives the net-absorption/secretion of fluid and, thus, the homeostasis of the liquid layer which lines pulmonary epithelia. A potential regulation of chloride transport processes by H2S is unknown in pulmonary epithelia and to be investigated in this project. In addition, there is an association between imbalanced ion transport in the airways and the airway disease cystic fibrosis. This disease is characterized, due to a mutation in a chloride channel, by a reduced chloride secretion, as well as an increased sodium absorption by airway epithelial cells. A modulation of both ion transport processes by H2S may have a pharmacological potential in the context of this disease. Therefore, novel H2S-liberating compounds will be characterized pharmacologically with respect to sodium and chloride transport processes in airway epithelia. In summary, we aim to obtain new insights into the regulation of pulmonary ion transport by the gasotransmitter H2S, as well as to extend these findings into the characterization of novel compounds with a pharmacological potential.

• DFG Programme: Research Grants
• International Connection: United Kingdom, USA
• Participating Persons: Dr. Deborah Baines; Dr. Khosrow Kashfi; Professor Dr. Wolfgang Kummer; Professor Dr. Kenneth Olson