Sphingolipids are potent lipid second messengers that regulate cell differentiation, migration, survival, and secretion, and alterations in sphingolipid signaling have been implicated in a variety of diseases. However, how sphingolipid levels are regulated, particularly in the nervous system, remains poorly understood. Here, we show that the generation of sphingosine-1-phosphate by sphingosine ...

The septohippocampal system has been implicated in the cognitive deficits associated with ethanol consumption, but the cellular basis of ethanol action awaits full elucidation. In the medial septum/diagonal band of Broca (MS/DB), a muscarinic tone, reflective of firing activity of resident cholinergic neurons, regulates that of their noncholinergic, putatively GABAergic, counterparts. Here we t...

Previous work from our laboratory indicates that bile acids, specifically lithocholic acid conjugates, interact with muscarinic receptors on gastric chief cells. Structural similarities between acetylcholine and lithocholyltaurine suggest a potential molecular basis for their interaction with the same receptor. We synthesized a hybrid molecule consisting of the steroid nucleus of lithocholyltau...

Acetylcholine is a transmitter in preganglionic autonomic and postganglionic parasympathetic nerves and a non-neuronal paracrine mediator in the alimentary tract. Acetylcholine is involved in the control of almost any function within these organ systems, and almost every cell type expresses multiple muscarinic receptor subtypes. Although muscarinic receptors at non-neuronal effector cells commo...

The olfactory bulb (OB) and piriform cortex receive dense cholinergic projections from the basal forebrain. Cholinergic modulation within the piriform cortex has long been proposed to serve important functions in olfactory learning and memory. We here investigate how olfactory discrimination learning is regulated by cholinergic modulation of the OB inputs to the piriform cortex. We examined rat...

Five different muscarinic receptor subtypes can be distinguished by the differences in their amino acid sequence, the coupled signal transduction system, pharmacological binding properties and activation of ionic fluxes. The present study served to characterize the binding profile of muscarinic receptors in human colon carcinoma cells (HT-29) using selective muscarinic antagonists. The affiniti...

Objective(s): Cells perform their functional activities by communicating with each other through endogenous substances and receptors. Post-translation, stem cells function properly in new host tissue by carrying specific cell surface receptors. We aimed to characterize muscarinic receptor subtypes in mesenchymal stem cells (MSCs) together with osteogenic and adipogenic...

In the present work we have investigated which muscarinic (M) receptor subtype is responsible for the steroidogenic effect of muscarinic agonists in bovine zona fasciculata-reticularis (ZFR) cells in culture. Radioligand binding studies using the muscarinic antagonist [(3)H]quinuclidinyl benzilate ([(3)H]QNB) demonstrated binding sites of high affinity (K(d)=0.45 nM) and low capacity ( approxim...

PURPOSE To determine the relative levels of the five muscarinic receptor subtypes in the anterior segment of the human eye. METHODS Antisera selective for each of the five muscarinic receptor proteins were incubated with [3H]-QNB bound receptors solubilized from human iris sphincter, ciliary muscle, and ciliary processes. Precipitation of the radiolabeled receptor-antibody complexes and scint...

Regulation of extracellular glutamate levels by muscarinic receptors in the striatum of unanesthetized rats was investigated by microdialysis. Extracellular glutamate levels were elevated by intrastriatal perfusion of L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), a competitive substrate of plasma membrane excitatory amino acid transporters. The nonselective muscarinic agonist, oxotre...