Is modulation of nicotinic acetylcholine receptors by melatonin relevant for therapy with cholinergic drugs?
Melatonin, the darkness hormone, synchronizes several physiological functions to light/dark cycle. Besides the awake/sleep cycle that is intuitively linked to day/night, daily variations in memory acquisition and innate or acquired immune responses are some of the major activities linked to melatonin rhythm. The daily variation of these complex processes is due to changes in specific mechanisms. In the last years we focused on the influence of melatonin on the expression and function of nicotinic acetylcholine receptors (nAChRs). Melatonin, either "in vivo" or "in vitro", increases, in a selective manner, the efficiency of alpha-bungarotoxin (alpha-BTX)-sensitive nAChRs. Melatonin's effect on receptors located in rat sympathetic nerve terminals, cerebellum, skeletal muscle and chick retina, was tested. We observed that melatonin is essential for the development of alpha-BTX-sensitive nAChRs, and important for receptor maintenance in aging models. Taking into account that both melatonin and alpha-7 nAChRs (one of the subtypes sensitive to alpha-BTX) are involved in the development of Alzheimer's disease, here we discuss the possibility of a therapeutic strategy focused on both melatonin replacement and its potential association with cholinergic drugs.
Markus
Regina P
RP
Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, Universidade de São Paulo, Brazil. rpmarkus@usp.br
Silva
Claudia L M
CL
Franco
Daiane Gil
DG
Barbosa
Eduardo Mortani
EM
Ferreira
Zulma S
ZS
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D018678:Cholinergic Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D006801:Humans; D008550:Melatonin / Q000008:administration & dosage* / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018678:Cholinergic Agents; D011978:Receptors, Nicotinic; D008550:Melatonin