Search results for "Cholinergic"

Vesicular Storage and Release of Cholinergic False Transmitters

1979

Publisher Summary Several analogues of choline are known, which are taken up by cholinergic nerve terminals and released in the acetylated form on stimulation. Such compounds are thus precursors of cholinergic false transmitters. This chapter discusses two compounds, N-methyl-N-2-hydroxyethylpyrrolidiniu (mPCh) and homocholine (HCh), using guinea-pig cortex and the electric organ of Torpedo marmorata. In the experiments with cortex, the false transmitter precursors were injected into the tissue and released transmitters collected in Locke solution applied to the surface of the cortex in plastic sleeves. Free vesicles and those attached to external membranes were isolated from tissue subjace…

The Uptake of Acetylpyrrolidinecholine — A False Cholinergic Transmitter — Into Mammalian Cerebral Cortical Synaptic Vesicles

1978

It is now well established that cholinergic vesicles are metabolically heterogeneous organelles. It is, however, still under discussion whether this is due to an intravesicular or an intervesicular heterogeneity. March-banks and Israel (10), supporting the hypothesis of intravesicular heterogeneity, suggested that newly formed ACh is only loosely bound to the vesicles. On the other hand, a distinct vesicle fraction obtained from the electromotor system of Torpedo marmorata after its incubation with radioisotopes shows a high specific radioactivity (12), results which favor the view that intervesicular differences do exist. Biochemical and morphological findings suggest that these vesicles h…

Allosteric modulation of nicotinic acetylcholine receptors as a treatment strategy for Alzheimer's disease

2000

The basic symptoms of Alzheimer's dementia, i.e., a loss in cognitive function, are due to impaired nicotinic cholinergic neurotransmission. To compensate for this impairment by drug treatment, blockers of the acetylcholine-degrading enzyme acetylcholinesterase are applied, even though this approach obviously is prone to many side-effects, including those of muscarinic nature. We have recently described a novel class of nicotinic acetylcholine receptor ligands which, similar to the action of benzodiazepines on GABA(A) receptors, allosterically potentiate submaximal nicotinic responses. The sensitizing effect is a consequence of facilitated channel opening in the presence of allosterically p…

Decreased response to acetylcholine during aging of Aplysia neuron R15

2013

How aging affects the communication between neurons is poorly understood. To address this question, we have studied the electrophysiological properties of identified neuron R15 of the marine mollusk Aplysia californica . R15 is a bursting neuron in the abdominal ganglia of the central nervous system and is implicated in reproduction, water balance, and heart function. Exposure to acetylcholine (ACh) causes an increase in R15 burst firing. Whole-cell recordings of R15 in the intact ganglia dissected from mature and old Aplysia showed specific changes in burst firing and properties of action potentials induced by ACh. We found that while there were no significant changes in resting membrane p…

Effects of Some Directly-Acting Smooth Muscle Relaxant Drugs on Isolated Human Preparations of the Upper Urinary Tract

1985

It is generally assumed that drugs which induce relaxation of smooth muscles may be of clinical importance in some urological disorders; such drugs are indeed widely used, for example in the therapy of unstable bladders or to facilitate the passage of ureteral stones. Antispasmodic action may be classified in neurotropic and musculo-tropic action; the former acting on the autonomic nervous system and the latter directly on smooth muscle cells. Examples for the first type of action are anticholinergic drugs or alpha-adrenoceptor-antagonists, whereas papaverine is a classic drug with the second type of action.

The non-neuronal cholinergic system

2012

Immunohistochemistry of cholinergic receptors.

1992

Acetylcholine and its receptors are involved in a variety of important signal transduction processes. As shown here paradigmatically for the human neuromuscular junction and the cerebral cortex, acetylcholine receptors can be visualized immunohistochemically at the cellular and subcellular level under physiological and pathological conditions. At normal motor endplates nicotinic cholinoceptors are localized at the surface of the postsynaptic junctional folds. In myasthenic syndromes investigation of muscle biopsies enables the diagnosis of receptor deficiencies at the ultrastructural level. In normal cerebral cortex pyramidal neurons are equipped with both nicotinic and muscarinic acetylcho…

Neuromuscular junction disassembly and muscle fatigue in mice lacking neurotrophin-4

2001

Neurotrophin-4 (NT-4) is produced by slow muscle fibers in an activity-dependent manner and promotes growth and remodeling of adult motorneuron innervation. However, both muscle fibers and motor neurons express NT-4 receptors, suggesting bidirectional NT-4 signaling at the neuromuscular junction. Mice lacking NT-4 displayed enlarged and fragmented neuromuscular junctions with disassembled postsynaptic acetylcholine receptor (AChR) clusters, reduced AChR binding, and acetylcholinesterase activity. Electromyographic responses, posttetanic potentiation, and action potential amplitude were also significantly reduced in muscle fibers from NT-4 knock-out mice. Slow-twitch soleus muscles from thes…

Functional evidence for GABA as modulator of the contractility of the longitudinal muscle in mouse duodenum: Role of GABAA and GABAC receptors

2007

We investigated, in vitro, the effects of gamma-aminobutyric acid (GABA) on the spontaneous mechanical activity of the longitudinal smooth muscle in mouse duodenum. GABA induced an excitatory effect, consisting in an increase in the basal tone, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABA(C)-receptor antagonist and it was not affected by phaclofen, a GABA(B)-receptor antagonist. Muscimol, GABA(A) receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA(C) …

Central cholinergic functions in human amyloid precursor protein knock-in/presenilin-1 transgenic mice.

2004

Alzheimer's disease is characterized by amyloid peptide formation and deposition, neurofibrillary tangles, central cholinergic dysfunction, and dementia; however, the relationship between these parameters is not well understood. We studied the effect of amyloid peptide formation and deposition on central cholinergic function in knock-in mice carrying the human amyloid precursor protein (APP) gene with the Swedish/London double mutation (APP-SL mice) which were crossbred with transgenic mice overexpressing normal (PS1wt) or mutated (M146L; PS1mut) human presenilin-1. APP-SLxPS1mut mice had increased levels of Abeta peptides at 10 months of age and amyloid plaques at 14 months of age while AP…