This flushing phenomenon is a typical pharmacological problem whereby desired and undesired effects arise simultaneously. Hence, the Bad Nauheim scientists set themselves the objective of understanding the mechanisms behind the desired and, in particular, undesired effects of nicotinic acid. The results of this study are to be published in the August issue of the Journal of Clinical Investigation.
Offermanns and his colleagues had already succeeded in identifying a specific receptor for nicotinic acid that conveys the desired effects of nicotinic acid. Tests on mice, in which the gene for this receptor had been deactivated, showed, however, that the receptor is also responsible for the nicotinic-acid-induced flushing reaction. "We have now succeeded in demonstrating that the receptor exists both in the main cells of the top layer of the skin or epidermis, which are called keratinocytes, and the immune cells, known as Langerhans cells, also found in the epidermis," reports Offermanns. By studying genetically modified mouse strains in which the receptor in either the Langerhans cells or keratinocytes is blocked, the Max Planck researchers were able to show that the first phase of the flushing reaction is triggered by the activation of Langerhans cells. In contrast, the second and longer phase results from the activation of the keratinocytes. In both phases, different prostaglandins are formed through the activation of the nicotinic acid rece
|Contact: Stefan Offermanns|