Determination of the chemical mechanism of neurotransmitter receptor-mediated reactions by rapid chemical kinetic methods.
AuthorsHess GP, Niu L, Wieboldt R
JournalAnn N Y Acad Sci
PubMed ID7611678
Fourier transform infrared (FTIR) spectroscopic investigation of the nicotinic acetylcholine receptor (nAChR). Investigation of agonist binding and receptor conformational changes by flash-induced release of 'caged' carbamoylcholine.
AuthorsGörne-Tschelnokow U, Hucho F, Naumann D, Barth A, Mäntele W
JournalFEBS Lett
PubMed ID1505686
'The binding and interaction of carbamoylcholine with the nicotinic acetylcholine receptor was investigated using photolytically released carbamoylcholine (''caged'' carbamoylcholine). Upon UV flash activation of this photolabile substrate analog, characteristic changes in the IR absorbance spectrum were detected. Apart from difference bands arising from the changes of molecular structure upon photolytical ... More
Cocaine: mechanism of inhibition of a muscle acetylcholine receptor studied by a laser-pulse photolysis technique.
AuthorsNiu L, Abood LG, Hess GP
JournalProc Natl Acad Sci U S A
PubMed ID8618833
'Effects of cocaine on the muscle nicotinic acetylcholine receptor were investigated by using a chemical kinetic technique with a microsecond time resolution. This membrane-bound receptor regulates signal transmission between nerve and muscle cells, initiates muscle contraction, and is inhibited by cocaine, an abused drug. The inhibition mechanism is not well ... More
Synthesis, photochemistry, and biological activity of a caged photolabile acetylcholine receptor ligand.
AuthorsMilburn T, Matsubara N, Billington AP, Udgaonkar JB, Walker JW, Carpenter BK, Webb WW, Marque J, Denk W, McCray JA
JournalBiochemistry
PubMed ID2706267
'A biologically inert photolabile precursor of carbamoylcholine has been synthesized; it is photolyzed to carbamoylcholine, a well-characterized acetylcholine analogue, with a half-time of 40 microseconds at pH 7.0 and a quantum yield of 0.8. The compound, N-(alpha-carboxy-2-nitrobenzyl)carbamoylcholine, was synthesized from (2-nitrophenyl)glycine. The photolysis rates (of five compounds) and the biological ... More
Functional mapping and Ca2+ regulation of nicotinic acetylcholine receptor channels in rat hippocampal CA1 neurons.
AuthorsKhiroug L, Giniatullin R, Klein RC, Fayuk D, Yakel JL
JournalJ Neurosci
PubMed ID14534236
'Diverse subtypes of nicotinic acetylcholine receptors (nAChRs), including fast-desensitizing alpha7-containing receptors thought to be Ca2+-permeable, are expressed in the CNS, where they appear to regulate cognitive processing and synaptic plasticity. To understand the physiological role of nAChRs in regulating neuronal excitability, it is important to know the distribution of functional ... More
Determination of the chemical mechanism of neurotransmitter receptor-mediated reactions by rapid chemical kinetic techniques.
AuthorsHess GP
JournalBiochemistry
PubMed ID8381026
'Rapid chemical reaction techniques play an important role in unraveling the mechanism of reactions mediated by soluble proteins, including enzymes involved in the regulation of intracellular processes and the biosynthesis of proteins and nucleic acids. Regulatory proteins change conformation rapidly and must, therefore, be studied in the microsecond-to-millisecond time region. ... More
Two-photon scanning photochemical microscopy: mapping ligand-gated ion channel distributions.
AuthorsDenk W
JournalProc Natl Acad Sci U S A
PubMed ID7517555
'The locations and densities of ionotropic membrane receptors, which are responsible for receiving synaptic transmission throughout the nervous system, are of prime importance in understanding the function of neural circuits. It is shown that the highly localized liberation of "caged" neurotransmitters by two-photon absorption-mediated photoactivation can be used in conjunction ... More
Development and application of caged ligands for neurotransmitter receptors in transient kinetic and neuronal circuit mapping studies.
AuthorsHess GP, Grewer C
JournalMethods Enzymol
PubMed ID9661164
Chemical kinetic investigations of the channel-opening process of neurotransmitter receptors.
AuthorsMatsubara N, Billington AP, Chen HC, Guzikowski AP, Johnson KW, Ramesh D, Sweet MT, Hess GP
JournalAdv Exp Med Biol
PubMed ID1722073
Synthesis, photochemistry, and biological characterization of photolabile protecting groups for carboxylic acids and neurotransmitters.
AuthorsGee KR, Carpenter BK, Hess GP
JournalMethods Enzymol
PubMed ID9661143
Caged compounds: photorelease technology for control of cellular chemistry and physiology.
AuthorsEllis-Davies GC
JournalNat Methods
PubMed ID17664946
Caged compounds are light-sensitive probes that functionally encapsulate biomolecules in an inactive form. Irradiation liberates the trapped molecule, permitting targeted perturbation of a biological process. Uncaging technology and fluorescence microscopy are 'optically orthogonal': the former allows control, and the latter, observation of cellular function. Used in conjunction with other technologies ... More
Anatomical and functional imaging of neurons using 2-photon laser scanning microscopy.
AuthorsDenk W, Delaney KR, Gelperin A, Kleinfeld D, Strowbridge BW, Tank DW, Yuste R
JournalJ Neurosci Methods
PubMed ID7869748
Light scattering by brain tissue and phototoxicity are major obstacles to the use of high-resolution optical imaging and photo-activation ('uncaging') of bioactive compounds from inactive ('caged') precursors in intact and semi-intact nervous systems. Optical methods based on 2-photon excitation promise to reduce these obstacles (Denk, 1994; Denk et al., 1990, ... More
Long distance communication between muscarinic receptors and Ca2+ release channels revealed by carbachol uncaging in cell-attached patch pipette.
AuthorsAshby MC, Camello-Almaraz C, Gerasimenko OV, Petersen OH, Tepikin AV
JournalJ Biol Chem
PubMed ID12657637
We have investigated the characteristics of cytosolic Ca2+ signals induced by muscarinic receptor activation of pancreatic acinar cells that reside within intact pancreatic tissue. We show that these cells exhibit global Ca2+ waves and local apical Ca2+ spikes. This is the first evidence for local Ca2+ signaling in undissociated pancreatic ... More
Rapid chemical kinetic techniques for investigations of neurotransmitter receptors expressed in Xenopus oocytes.
AuthorsNiu L, Vazquez RW, Nagel G, Friedrich T, Bamberg E, Oswald RE, Hess GP
JournalProc Natl Acad Sci U S A
PubMed ID8917527
Xenopus laevis oocytes have been used extensively during the past decade to express and study neurotransmitter receptors of various origins and subunit composition and also to express and study receptors altered by site-specific mutations. Interpretations of the effects of structural differences on receptor mechanisms were, however, hampered by a lack ... More
Mechanism-based discovery of ligands that counteract inhibition of the nicotinic acetylcholine receptor by cocaine and MK-801.
AuthorsHess GP, Ulrich H, Breitinger HG, Niu L, Gameiro AM, Grewer C, Srivastava S, Ippolito JE, Lee SM, Jayaraman V, Coombs SE
JournalProc Natl Acad Sci U S A
PubMed ID11095713
Nicotinic acetylcholine receptors (AChR) belong to a family of proteins that form ligand-gated transmembrane ion channels. They are involved in the fast transmission of signals between cells and the control of intercellular communication in the nervous system. A variety of therapeutic agents and abused drugs, including cocaine, inhibit the AChR ... More
An acetylcholine receptor regulatory site in BC3H1 cells: characterized by laser-pulse photolysis in the microsecond-to-millisecond time region.
AuthorsNiu L, Hess GP
JournalBiochemistry
PubMed ID8471597
When a neurotransmitter binds to its specific receptor, the protein forms transmembrane channels through which ions flow, leading to changes in transmembrane voltage that trigger signal transmission between neurons. How do inhibitors affect this process? Interesting and extensive information comes from investigations of the acetylcholine receptor, the best known of ... More
Biochemical evaluation of photolabile precursors of choline and of carbamylcholine for potential time-resolved crystallographic studies on cholinesterases.
AuthorsPeng L, Silman I, Sussman J, Goeldner M
JournalBiochemistry
PubMed ID8718877
Acetylcholinesterase and butyrylcholinesterase both rapidly hydrolyze the neurotransmitter acetylcholine. The unusual three-dimensional structure of acetylcholinesterase, in which the active site is located at the bottom of a deep and narrow gorge, raises cogent questions concerning traffic of the substrate, acetylcholine, and the products, choline and acetate, to and from the ... More
On the mechanism of inhibition of the nicotinic acetylcholine receptor by the anticonvulsant MK-801 investigated by laser-pulse photolysis in the microsecond-to-millisecond time region.
AuthorsGrewer C, Hess GP
JournalBiochemistry
PubMed ID10387024
The mechanism of inhibition of the muscle nicotinic acetylcholine receptor is of interest because of the many drugs which are known to modify its function. The laser-pulse photolysis technique, using a photolabile, biologically inert ligand (caged carbamoylcholine) for the nicotinic acetylcholine receptor, and BC3H1 cells have been used to investigate ... More
How fast does an acetylcholine receptor channel open? Laser-pulse photolysis of an inactive precursor of carbamoylcholine in the microsecond time region with BC3H1 cells.
AuthorsMatsubara N, Billington AP, Hess GP
JournalBiochemistry
PubMed ID1610795
The integrated function of the nervous system depends on specific and rapid transmission of signals between its constituent cells. The nicotinic acetylcholine receptor is the best known of a group of membrane-bound proteins responsible for such transmission; for this process to occur, a specific neurotransmitter, in this case acetylcholine, must ... More