Endocrine Abstracts

Introduction: Dolichols are isoprenoids, which are synthesized from acetyl-CoA via mevalonic acid, and they are known to be abundant in endocrine system. Adrenal medulla, which is not only an endocrine organ but also an organ derived from neural crest, secrets catecholamines via sodium and subsequent calcium influxes into the cells through nicotinic ACh receptor-operated cation channels and voltage-sensitive calcium channels, respectively, when the medulla is stimulated by acetylcholine (ACh). In this study, therefore, we investigated the role of dolichols and other isoprenoids in ACh-evoked catecholamine secretion from bovine adrenal chromaffin cells.

Results and Discussion: The treatment of the adrenal chromaffin cells with dolichols did not affect the ACh-evoked secretion of catecholamines. However, fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase which is a key enzyme in the isoprenoids’ synthesis, attenuated the ACh-evoked catecholamine secretion from the cells. The statin also reduced both thebACh-induced sodium and calcium influxes into the cells. Under the condition, the production of some isoprenoids in the cells is presumed to be very low. Mevalonate or geranylgeraniol, an alcohol type of geranylgeranyl pyrophosphate (GGPP), overcome the statin inhibition of catecholamine secretion, but not other isoprenoids, isopentenyl pyrophosphate, GGPP, geraniol, farnesol, farnesyl pyrophosphate, cholesterol and dolichols. Fluvastatin affected neither the expression of α3 and β4 nicotinic ACh receptors mRNA nor of voltage-sensitive calcium channel mRNA in the chromaffin cells. Two-dimensional electrophoresis showed that there was no difference between the protein quantity in the control and the fluvastatin-treated cells. These results strongly suggest that geranylgeraniols and/or GGPP in the membranes are essential for calcium-dependent catecholamine secretion in adrenal chromaffin cells.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.