Statins prevent cholinesterase inhibitor blockade of sympathetic α7-nAChR-mediated currents in rat superior cervical ganglion neurons
| Autor: | Mansoor Mozayan, Tony J.-F. Lee |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
Nicotine Superior cervical ganglion medicine.medical_specialty Sympathetic nervous system Patch-Clamp Techniques alpha7 Nicotinic Acetylcholine Receptor Physiology Superior Cervical Ganglion Receptors Nicotinic Choline Rats Sprague-Dawley Physiology (medical) Internal medicine medicine Galantamine Animals Dementia Vascular dementia Evoked Potentials Cells Cultured Neurons Dose-Response Relationship Drug business.industry medicine.disease Rats Blockade medicine.anatomical_structure Endocrinology Cholinesterase Inhibitors Neuron Hydroxymethylglutaryl-CoA Reductase Inhibitors Alzheimer's disease Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 293:H1737-H1744 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00269.2007 |
| Popis: | Statins are reported to be beneficial in treating a multitude of disorders including dementia due to Alzheimer disease (AD) and vascular dementia (VaD) with varying, yet-to-be determined mechanisms of actions. Although cholinesterase inhibitors (ChEIs) are still recommended as the primary drug of choice for AD and related diseases, their efficacy is frequently questioned. We recently reported that α7-neuronal acetylcholine nicotinic receptor (α7-nAChR)-mediated neurogenic vasodilation of porcine cerebral arteries was blocked by ChEIs, and this blockade was prevented by statin pretreatment. The exact mechanism of interaction between ChEIs and statins remains unclear. Activation of α7-nAChRs located on perivascular postganglionic sympathetic nerve terminals releases norepinephrine, which then acts on presynaptic β2-adrenoceptors located on neighboring nitrergic nerve terminals, resulting in nitric oxide release and vasodilation. The present study, therefore, was designed to determine whether interaction of ChEIs and statins occurs at the α7-nAChR level. We examined effects of concurrent application of ChEIs and statins on α7-nAChR-mediated inward currents in primary neuronal cultures of rat superior cervical ganglion cells, the origin of the perivascular sympathetic innervation to the cerebral arteries. The results indicated that physostigmine, neostigmine, and galantamine inhibited choline- and nicotine-induced whole cell currents in a concentration-dependent manner. This inhibition, which was noncompetitive in nature, was prevented by concurrent application of mevastatin and lovastatin in a concentration-dependent manner. These results suggest that statins protect α7-nAChR function directly at the receptor level. Since α7-nAChR is neuroprotective, having beneficial effects on memory and cerebral vascular function, its functional inhibition by ChEIs may explain in part the limitation of its effectiveness in AD and VaD therapy. Protection of α7-nAChR function from ChEI inhibition by concurrent administration of statins may provide an alternative strategy in improving the efficacy of AD and VaD therapy. |
| Databáze: | OpenAIRE |
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