Search results for "Nicotinic"
showing 10 items of 189 documents
Cellular Distribution and Expression of Cortical Acetylcholine Receptors in Aging and Alzheimer's Disease
1991
Ligand binding studies show marked reductions of nicotinic, but not of muscarinic binding sites in Alzheimer's disease. Using monoclonal antibodies we studied immunohistochemically the expression of the respective receptor proteins in the frontal cortex of middle-aged (55 +/- 5 yr) controls, age-matched controls (73 +/- 6 yr), and patients with Alzheimer's disease (74 +/- 5 yr). Density of nicotinic cholinoceptive neurons was 8000/mm3 for middle-aged controls and 4000/mm3 for age-matched controls, but only 900/mm3 in Alzheimer's brains (p less than 0.0001). Densities of muscarinic cholinoceptive and of Nissl-stained neurons were not significantly different between the groups, pointing to a …
Chapter 9 Nicotinic acetylcholine receptors on hippocampal neurons: cell compartment-specific expression and modulatory control of channel activity
1996
Publisher Summary The neuronal nicotinic acetylcholine receptors (nAChRs) are differentially expressed on the somato-dendritic surface of hippocampal neurons. This chapter demonstrates that various ions and drugs play a crucial role in modulating the activity of neuronal nAChRs. Considering the diversity of the neurotransmitter receptors and their binding sites and the diversity of substances, which can act simultaneously as a primary agonist of one receptor and an allosteric modulator of a different receptor, an enormous variety of combinatorial possibilities can be achieved in the brain giving rise to very complex neuronal networks. The characterization of the diversity of many receptors …
Neuronal nicotinic receptors in synaptic functions in humans and rats: physiological and clinical relevance.
2000
The present report describes the participation of nicotinic receptors (nAChRs) in controlling the excitability of local neuronal circuitries in the rat hippocampus and in the human cerebral cortex. The patch-clamp technique was used to record responses triggered by the non-selective agonist ACh and the alpha7-nAChR-selective agonist choline in interneurons of human cerebral cortical and rat hippocampal slices. Evidence is provided that functional alpha7- and alpha4beta2-like nAChRs are present on somatodendritic and/or preterminal/terminal regions of interneurons in the CA1 field of the rat hippocampus and in the human cerebral cortex and that activation of the different nAChR subtypes pres…
Na+ ions binding to the bradykinin B2 receptor suppress agonist-independent receptor activation.
1996
Control of the balance between receptor activation and inactivation is a prerequisite for seven transmembrane domain (7TM) receptor function. We asked for a mechanism to stabilize the inactive receptor conformation which prevents agonist-independent receptor activation. Na+ ions have reciprocal effects on agonist versus antagonist interaction with various 7TM receptors. To investigate the Na+ dependence of receptor activation we chose the bradykinin B2 receptor as a prototypic 7TM receptor. Decrease of the intracellular Na+ content from 40 mM to 10 mM of COS-1 cells transiently expressing rat B2 receptors activated the B2 receptor in the absence of agonist as shown by a 3-fold increase in t…
Behavioral effects of different enriched environments in mice treated with the cholinergic agonist PNU-282987.
2013
Abstract Environmental enrichment is an experimental model in which rodents are housed in complex environments that favor lower levels of anxiety-like behavior. PNU-282987 (PNU) is a α7 nicotinic acetylcholine receptor agonist with beneficial effects on learning though its effects on anxiety are unclear. Our main aim was to carry out a study of its effects in NMRI ( n = 96) mice reared in different environments: environmental enrichment (EE), Marlau™ cages (MC) and standard environment (SE). After a 4-month period, mice received acute treatment of PNU (2.5, 5 and 10 mg/kg) and were evaluated in the elevated plus-maze (EPM) and hole-board (HB). In the EPM, both EE and MC reared mice showed …
Involvement of tachykinin NK2 receptors in the modulation of spontaneous motility in rat proximal colon.
2000
The role of endogenous tachykinins and the mechanisms whereby they act on NK2 receptors, modulating spontaneous motility, were investigated in rat isolated proximal colon. The mechanical activity was detected as changes in intraluminal pressure. The NK2 receptor antagonist, MEN 10627, produced a concentration-dependent reduction of the contraction amplitude. [beta-Ala8]-neurokinin A(4-10), an NK2 receptor agonist, and [Sar9, Met(O2)11]-Substance P ([Sar9, Met(O2)11]-SP), an NK1 receptor agonist, induced a concentration-dependent contractile response, characterized by an increase in basal tone with superimposed phasic contractions. MEN 10627 antagonized the response to [beta-Ala8]-neurokinin…
Involvement of cholinergic nicotinic receptors in the menthol-induced gastric relaxation.
2014
We have previously demonstrated that menthol reduces murine gastric tone in part through a neural mechanism, involving adrenergic pathways and reduction of ongoing release of acetylcholine from enteric nerves. In the present study we aimed to verify whether the gastric relaxation to menthol may be triggered by interaction with neural receptors or ionic channels proteins, such as transient receptor potential (TRP)-melastatin8 (TRPM8), TRP-ankyrin 1 (TRPA1), 5-hydroxytriptamine 3 (5-HT3) receptor or cholinergic nicotinic receptors. Spontaneous mechanical activity was detected in vitro as changes in intraluminal pressure from isolated mouse stomach. Menthol (0.3-30 mM) induced gastric relaxati…
Choline is a Selective Agonist of α7 Nicotinic Acetylcholine Receptors in the Rat Brain Neurons
1998
In the present study, we demonstrate that choline, a precursor of acetylcholine (ACh) and a product of acetylcholine hydrolysis by acetylcholinesterase (AChE), acts as an efficient and relatively selective agonist of alpha7-containing nicotinic acetylcholine receptors (nAChR) in neurons cultured from the rat hippocampus, olfactory bulb and thalamus as well as in PC12 cells. Choline was able to activate postsynaptic and presynaptic alpha7 nAChRs, with the latter action resulting in the release of other neurotransmitters. Although choline was approximately one order of magnitude less potent than ACh (EC50 of 1.6 mM for choline and 0.13 mM for ACh), it acted as a full agonist at alpha7 nAChRs.…
Introductory Lecture: Allosteric Modulation of Torpedo Nicotinic Acetylcholine Receptor Ion Channel Activity by Noncompetitive Agonists
1997
AbstractSimilar to other neuroreceptors of the vertebrate central nervous system, the nicotinic acetylcholine receptor (nAChR) is subject to modulatory control by allosterically acting ligands. Of particular interest in this regard are allosteric ligands that enhance the sensitivity of the receptor to its natural agonist acetylcholine (ACh), as such ligands could be useful as drugs in diseases associated with impaired nicotinic neurotransmission. Here we discuss the action of a novel class of nAChR ligands which act as allosterically potentiating ligands (APL) on the nicotinic responses induced by ACh and competitive agonists. In addition, APLs also act as noncompetitive agonists of very lo…
Allosteric modulation of nicotinic receptors as a treatment strategy for Alzheimer's disease.
2000
Impairment of the central cholinergic system has a pivotal role in the cognitive decline observed in patients with Alzheimer’s disease (AD). One of the most prominent cholinergic deficits is the reduced number of nicotinic acetylcholine receptors (nAChR) in the brain. Since these receptors are important for memory and learning, enhancing nicotinic neurotransmission is a promising treatment strategy for AD. The two most common approaches to correcting these cholinergic deficits are to increase the synaptic availability of acetylcholine (ACh) by inhibiting acetylcholinesterase (AChE), or to mimic the effects of ACh (nicotinic agonists) by acting directly on nicotinic receptors. Clinical studi…