title: Functional coupling reactions of human amylin receptor and nicotinic acetylcholine receptors in rat brain neurons.
abstract: Human amylin (hAmylin) is co-released with insulin from pancreatic B-cells and the actions of this peptide on its target tissues maintain the cell excitability and glucose homeostasis. Inappropriate control of hAmylin secretion may result in human disease, particularly Alzheimer's disease (AD). It's unknown that which kind of receptor is activated by human amylin, leading to the neurotoxicity in neurons of brain. Nicotinic acetylcholine receptors (nAChRs) are known to play a critical role in a variety of nervous diseases. In the present study, we sought to determine the inter-relationships between these two receptors by examining the actions of hAmylin and nicotine on whole-cell currents and membrane potential in basal forebrain neurons. Whole cell patch-clamp recordings were performed on enzymatically dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. The results showed that either hAmylin or nicotine individually caused a dose-dependent (1 nmol/L-20 µmol/L) membrane depolarization and an increase in firing frequency of DBB neurons. Application of AC253, an amylin receptor antagonist, blocked the excitatory effects of not only hAmylin but also nicotine; dihydro-β-erythroidine (DHβE), a nAChR antagonist, also blocked the effects of nicotine and hAmylin. These electrophysiological results suggest that hAmylin receptor and nAChRs on DBB neurons are coupled and may function in a co-operative manner to influence the excitability of DBB neurons. This finding is important for us to understand the cause and mechanisms of AD.
authors.affiliation: Neurobiology Laboratory, Luohe Medical College, Luohe 462002, China. lizongming3@126.com
authors.forename: Zong-Ming
authors.initials: ZM
authors.lastname: Li
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Li
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D020667:Diagonal Band of Broca / Q000378:metabolism / Q000502:physiology; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058287:Receptors, Islet Amyloid Polypeptide / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*
chemical_list: D058228:Islet Amyloid Polypeptide; D058287:Receptors, Islet Amyloid Polypeptide; D011978:Receptors, Nicotinic; D009538:Nicotine