共查询到20条相似文献,搜索用时 31 毫秒
1.
Octopamine receptor subclasses were first proposed to explain differences in the pharmacological profiles of a range of physiological responses to octopamine obtained in the extensor-tibiae neuromuscular preparation of the locust. Thus, OCTOPAMINE1 receptors which inhibit an endogenous myogenic rhythm, increase intracellular calcium levels. Also OCTOPAMINE2 receptors which modulate neuromuscular transmission in this preparation, increase the level of adenylate cyclase activity. The current status of this classification is reviewed by examining the pharmacology of responses to octopamine in a range of preparations. It is concluded that the distinction between OCTOPAMINE1 and OCTOPAMINE2 receptor types is still valid, but that OCTOPAMINE2 receptors exhibit some tissue specific variations. Studies on a clonedDrosophila octopamine/tyramine (phenolamine) receptor are discussed and illustrate many of the difficulties presently encountered in making a definitive classification of octopamine receptors. These include the possibilities that single receptors may activate multiple second messenger systems and that different agonists may differentially couple the same receptor to different second messenger systems. 相似文献
2.
Identification and characterization of a novel family of Drosophila beta-adrenergic-like octopamine G-protein coupled receptors 总被引:1,自引:0,他引:1
Insect octopamine receptors carry out many functional roles traditionally associated with vertebrate adrenergic receptors. These include control of carbohydrate metabolism, modulation of muscular tension, modulation of sensory inputs and modulation of memory and learning. The activation of octopamine receptors mediating many of these actions leads to increases in the levels of cyclic AMP. However, to date none of the insect octopamine receptors that have been cloned have been convincingly shown to be capable of directly mediating selective and significant increases in cyclic AMP levels. Here we report on the identification and characterization of a novel, neuronally expressed family of three Drosophila G-protein coupled receptors that are selectively coupled to increases in intracellular cyclic AMP levels by octopamine. This group of receptors, DmOct beta1R (CG6919), DmOct beta2R (CG6989) and DmOct beta3R (CG7078) shows homology to vertebrate beta-adrenergic receptors. When expressed in Chinese hamster ovary cells all three receptors show a strong preference for octopamine over tyramine for the accumulation of cyclic AMP but show unique pharmacological profiles when tested with a range of synthetic agonists and antagonists. Thus, the pharmacological profile of individual insect tissue responses to octopamine might vary with the combination and the degree of expression of the individual octopamine receptors present. 相似文献
3.
James K. Wamsley 《Molecular neurobiology》1992,6(2-3):313-321
The axonal transport of neurotransmitter receptors is thought to be a common phenomenon in many neuronal systems. The “machinery”
for receptor (protein) “assembly” is found in the cell bodies of neurons and the “manufacture” of receptors takes place there.
These receptors are then “shipped” to their ultimate destinations by a transport process. This is an axonal transport mechanism
in the case of presynaptic receptors. Some form of transport process may also exist to send receptors out into the dendritic
arborizations of neurons, although the latter is more difficult to verify. Axonal transport has been demonstrated, in the
peripheral nervous systems, for many different neurotransmitter receptors. In the central nervous system, the results are
less clear, but indicate the presence of a transport mechanism for catecholamine, acetylcholine, and opiate sites. One important
component then, in the development of receptors, is the transportation to terminal membrane sites where they are ultimately
incorporated and available for interaction with neurotransmitters and drugs. 相似文献
4.
Jennie M. E. Cederholm Peter R. Schofield Trevor M. Lewis 《European biophysics journal : EBJ》2009,39(1):37-49
The Cys-loop receptor superfamily of ligand-gated ion channels has a prominent role in neuronal signalling. These receptors
are pentamers, each subunit containing ten β-strands in the extracellular domain and four α-helical transmembrane domains
(M1–M4). The M2 domain of each subunit lines the intrinsic ion channel pore and residues within the extracellular domain form
ligand binding sites. Ligand binding initiates a conformational change that opens the ion-selective pore. The coupling between
ligand binding in the extracellular domain and opening of the intrinsic ion channel pore located in the membrane is not fully
understood. Several loop structures, such as loop 2, the Cys-loop, the pre-M1 region and the M2–M3 loop have been implicated
in receptor activation. The current “conformational change wave” hypothesis suggests that binding of a ligand initiates a
rotation of the β-sheets around an axis that passes through the Cys-loop. Due to this rotation, the Cys-loop and loop 2 are
displaced. Movement of the M2–M3 loop then twists the M2 domain leading to a separation of the helices and opening of the
pore. The publication of a crystal structure of an acetylcholine binding protein and the refined structure of the Torpedo marmorata acetylcholine receptor have improved the understanding of the mechanisms and structures involved in coupling ligand binding
to channel gating. In this review, the most recent findings on some of these loop structures will be reported and discussed
in view of their role in the gating mechanism. 相似文献
5.
Nie H Li Z Lukas RJ Shen Y Song L Wang X Yin M 《Cellular and molecular neurobiology》2008,28(1):103-112
(1) Nicotinic acetylcholine receptors in central nervous system are thought to be new targets for Alzheimer’s disease. However,
the most involved nicotinic receptor subtype in Alzheimer’s disease is unclear. α4β2 receptor is the most widely spread subtype
in brain, involving in several important aspects of cognitive and other functions. We constructed cell line by transfecting
human amyloid precursor protein (695) gene into SH-EP1 cells which have been transfected with human nicotinic receptor α4
subunit and β2 subunit gene, to observe effects of α4β2 receptors activation on β-amyloid, expecting to provide a new cell
line for drug screening and research purpose. (2) Liposome transfection was used to express human amyloid precursor protein
(695) gene in SH-EP1-α4β2 cells. Function of the transfected α4β2 receptors was tested by patch clamp. Effects of nicotine
and epibatidine (selective α4β2 nicotinic receptor agonist) on β-amyloid were detected by Western blot and ELISA. Effects
of nicotine and epibatidine on amyloid precursor protein (695) mRNA level were measured using real-time PCR. (3) Human amyloid
precursor protein (695) gene was stably expressed in SH-EP1-α4β2 cells; Nicotine (1 μM) and epibatidine (0.1 μM) decreased
intracellular and secreted β-amyloid in the cells; and activation of α4β2 receptors did not affect amyloid precursor protein
(695) mRNA level. (4) These results suggest that the constructed cell line, expressing both amyloid precursor protein (695)
gene and human nicotinic receptor α4 subunit and β2 subunit gene, might be useful for screening specific nicotinic receptor
agonists against Alzheimer’s disease. Alteration of Aβ level induced by activation of α4β2 nAChR in our study might occur
at a post-translational level. 相似文献
6.
Allosteric potentiation of acetylcholine nicotinic receptors is considered to be one of the most promising approaches for
the treatment of Alzheimer’s disease. However, the exact localization of the allosteric binding site and the potentiation
mechanism at the molecular level are presently unknown. We have performed the “blind docking” of three known allosteric modulators
(galanthamine, codeine and eserine) with the Acetylcholine Binding Protein and models of human α7, α3β4 and α4β2 nicotinic
receptors, created by homology modeling. Three putative binding sites were identified in the channel pore, each one showing
different affinities for the ligands. One of these sites is localized opposite to the agonist binding site and is probably
implicated in the potentiation process. On the basis of these results, a possible mechanism for nicotinic acetylcholine receptor
(nAChRs) activation is proposed. The present findings may represent an important advance for understanding the allosteric
modulation mechanism of nAChRs.
Electronic supplementary material Supplementary material is available for this article at 相似文献
7.
The cephalochordate amphioxus (Branchiostoma floridae) has recently been placed as the most basal of all the chordates, which makes it an ideal organism for studying the molecular
basis of the evolutionary transition from invertebrates to vertebrates. The biogenic amine, dopamine regulates many aspects
of motor control in both vertebrates and invertebrates, and in both cases, its receptors can be divided into two main groups
(D1 and D2) based on sequence similarity, ligand affinity and effector coupling. A bioinformatic study shows that amphioxus
has at least three dopamine D1-like receptor sequences. We have recently characterized one of these receptors, AmphiD1/β,
which was found to have high levels of sequence similarity to both vertebrate D1 receptors and to β-adrenergic receptors,
but functionally appeared to be a vertebrate-type dopamine D1 receptor. Here, we report on the cloning of two further dopamine D1 receptors (AmphiAmR1 and AmphiAmR2) from adult amphioxus cDNA libraries and their pharmacological characterisation subsequent
to their expression in cell lines. AmphiAmR1 shows closer structural similarities to vertebrate D1-like receptors but shows some pharmacological similarities to invertebrate “DOP1” dopamine D1-like receptors. In contrast, AmphiAmR2 shows closer structural and pharmacological similarities to invertebrate “INDR”-like
dopamine D1-like receptors. 相似文献
8.
A. Donny Strosberg 《Molecular neurobiology》1990,4(3-4):211-250
The emergence of Biotechnology has provided pharmacologists with a variety of methods for investigating the structure, the
function, and the regulation of membrane-bound receptors with a precision that was not imagined even five years ago. These
new tools have been developed and used to analyze the known catecholamine β1- and β2 receptors and to discover and study a new subtype, the β-adrenergic receptor. We review here the salient features of each
of these three receptors, compare their structural and functional properties, and propose models to explain their differential
regulation in time and space.
A whole family of proteins has now been found to share with the β-adrenergic receptors their most prominent features, including
seven transmembrane domains and coupling with GTP-binding “G” proteins. We therefore propose that the biotechnology-based
procedures developed for the β-adrenergic receptors will be well applicable to the other members of this “R7G” family of receptors. 相似文献
9.
Little is known about the evolutionary relationship between vertebrate adrenergic receptors and invertebrate octopamine and tyramine receptors. The complexity of the adrenergic signalling system is believed to be an innovation of the vertebrate lineage but the presence of noradrenaline has been reported in some invertebrate species. The cephalochordate, amphioxus (Branchiostoma floridae), is an ideal model organism for studying the evolution of vertebrate GPCRs, given its unique position at the base of the chordate lineage. Here, we describe the pharmacological characterisation and second messenger coupling abilities of AmphiAmR4, which clusters with α2-adrenergic receptors in a phylogenetic tree but also shares a high sequence similarity to invertebrate octopamine/tyramine receptors in both BLAST and Hidden Markov Model analyses. Thus, it was of particular interest to determine if AmphiAmR4 displayed similar functional properties to the vertebrate α2-adrenergic receptors or to invertebrate octopamine or tyramine receptors. When stably expressed in Chinese hamster ovary (CHO) cells, noradrenaline couples the receptor to both the activation of adenylyl cyclase and to the activation of the MAPKinase pathway. Pharmacological studies with a wide range of agonists and antagonists suggest that AmphiAmR4 functions as an α2-adrenergic-like receptor when expressed in CHO cells. 相似文献
10.
11.
Coutinho-Silva R Monteiro da Cruz C Persechini PM Ojcius DM 《Purinergic signalling》2007,3(1-2):83-90
A growing number of studies have demonstrated the importance of ATPe-signalling via P2 receptors as an important component of the inflammatory response to infection. More recent studies have
shown that ATPe can also have a direct effect on infection by intracellular pathogens, by modulating membrane trafficking in cells that contain
vacuoles that harbour intracellular pathogens, such as mycobacteria and chlamydiae. A conserved mechanism appears to be involved
in controlling infection by both of these pathogens, as a role for phospholipase D in inducing fusion between lysosomes and
the vacuoles has been demonstrated. Other P2-dependent mechanisms are most likely operative in the cases of pathogens, such
as Leishmania, which survive in an acidic phagolysosomal-like compartment. ATPe may function as a “danger signal” that alerts the immune system to the presence of intracellular pathogens that damage the
host cell, while different intracellular pathogens have evolved enzymes or other mechanisms to inhibit ATPe-mediated signalling, which should, thus, be viewed as virulence factors for these pathogens. 相似文献
12.
Farooqui T 《Neurochemical research》2007,32(9):1511-1529
Octopamine functions as a neuromodulator, neurotransmitter, and neurohormone in insect nervous systems. Octopamine has a prominent
role in influencing multiple physiological events: (a) as a neuromodulator, it regulates desensitization of sensory inputs,
arousal, initiation, and maintenance of various rhythmic behaviors and complex behaviors such as learning and memory; (b)
as a neurotransmitter, it regulates endocrine gland activity; and (c) as a neurohormone, it induces mobilization of lipids
and carbohydrates. Octopamine exerts its effects by binding to specific proteins that belong to the superfamily of G protein-coupled
receptors and share the structural motif of seven transmembrane domains. The activation of octopamine receptors is coupled
with different second messenger pathways depending on species, tissue source, receptor type and cell line used for the expression
of cloned receptor. The second messengers include adenosine 3′,5′-cyclic monophosphate (cAMP), calcium, diacylglycerol (DAG),
and inositol 1,4,5-trisphosphate (IP3). The cAMP activates protein kinase A, calcium and DAG activate protein kinase C, and IP3 mobilizes calcium from intracellular stores. Octopamine-mediated generation of these second messengers is associated with
changes in cellular response affecting insect behaviors. The main objective of this review is to discuss significance of octopamine-mediated
neuromodulation in insect sensory systems. 相似文献
13.
Summary Glycine is one of the essential neurotransmitters modulating visual signals in retina. Glycine activates Cl- permeable receptors that conduct either inhibitory or excitatory actions, depending on the Cl− electrical–chemical gradient (E
Cl) positive or negative to the resting potential in the cells. Interestingly, both glycine-induced inhibitory and excitatory
responses are present in adult retinas, and the effects are confined in the inner and outer retinal neurons. Glycine inhibits
glutamate synapses in the inner plexiform layer (IPL), resulting in shaping light responses in ganglion cells. In contrast,
glycine excites horizontal cells and On-bipolar dendrites in the outer plexiform layer (OPL). The function of glycinergic
synapse in the outer retina represents the effect of network feedback from a group of centrifugal neurons, glycinergic interplexiform
cells. Moreover, immunocytochemical studies identify glycine receptor subunits (α1, α2, α3 and β) in retinas, forming picrotoxin-sensitive α-homomeric and picrotoxin-insensitive α/β-heteromeric receptors. Glycine receptors are modulated by intracellular Ca2+ and protein kinas C and A pathways. Extracellular Zn2+ regulates glycine receptors in a concentration-dependent manner, nanomolar Zn2+ enhancing glycine responses, and micromolar Zn2+ suppressing glycine responses in retinal neurons. These studies describe the function and mechanism of glycinergic synapses
in retinas. 相似文献
14.
Hein L 《Cell and tissue research》2006,326(2):541-551
The adrenergic system is an essential regulator of neuronal, endocrine, cardiovascular, vegetative, and metabolic functions. The endogenous catecholamines epinephrine and norepinephrine activate G-protein-coupled receptors to transmit their signal across the plasma membrane. These adrenoceptors can be divided into three different groups: the α1-receptors (α1A, α1B, α1D), α2-receptors (α2A, α2B, α2C), and β-receptors (β1, β2, β3). This review summarizes recent findings in the field of adrenoceptor signaling in neurons and includes a discussion of receptor-associated proteins, receptor dimerization, subcellular trafficking, and fluorescence optical methods for studying the kinetics of adrenergic signaling. Spatio-temporal imaging may become an important future tool for identifying the physiological significance of these complex signaling mechanisms in vivo. Gene-targeted mouse models carrying deletions in α2-adrenoceptor have provided detailed insights into specific neuronal functions of the three α2-receptor subtypes. 相似文献
15.
N. N. Dygalo A. A. Yushkova T. S. Kalinina N. Yu. Surnina L. B. Mel’nikova G. T. Shishkina 《Russian Journal of Developmental Biology》2000,31(1):43-46
We studied the level of noradrenaline and the density of α2-and β-adrenoreceptors in the brain stem and cerebral cortex of
12-day- and 21-day-old rat fetuses, as well as of rats at the ages of 1, 2, 5, 7, 9, 16, 21, 35, and 70 days. We found a positive
correlation between the level of noradrenaline in the brain stem and the density of β-receptors in the cerebral cortex, and
between the amount of α2- and β-receptors in the cerebral cortex, as well as between the values of each of these indices of
the neurochemical system and body weight. Significant negative correlations (r=−0.72 andr=−0.88, respectively) were found between the amount of α2-adrenoreceptors in the brain stem and the content of noradrenaline
in this brain region, as well as in the cerebral cortex. Explanations of these positive and negative correlations between
the level of noradrenaline and the amount of adrenergic receptors in the rat brain during ontogenesis are discussed. 相似文献
16.
Anita Sidhu 《Molecular neurobiology》1998,16(2):125-134
Dopamine receptors are a subclass of the super family of G protein-coupled receptors, that transduce their effects by coupling
to specific G proteins. Within the dopamine receptor family, the adenylyl cyclase stimulatory receptors include the D1 and D5 subtypes. The D1 and D5 dopamine receptors are genetically distinct, sharing >80% sequence homology within the highly conserved seven transmembrane
spanning domains, but displaying only 50% overall homology at the amino acid level. When expressed in transfected GH4C1 rat pituitary cells, both D1 and D5 receptors stimulate adenylyl cyclase and have identical affinities toward dopaminergic agonists and antagonists. In order
to analyze specific signaling pathways mediated by activation of either D1 or D5 receptors, we have identified the G proteins that are coupled to these receptors. Through functional analyses and competition
binding studies, and from immunoprecipitation techniques, using antisera against the various α subunits of G proteins, we
have established that both D1 and D5 receptors couple to Gsα. In addition, D1 receptors are also coupled to Goα. Since Goα has been implicated in the regulation of Ca2+, K+, and Na+ channels, this finding would suggest that D1 receptors can mediate the functional activity of these ion channels. There is also evidence to indicate that D5 receptors couple to Gzα, a novel G protein abundantly expressed in neurons. Thus, despite similar pharmacological properties, such differential
coupling of D1 and D5 receptors to G proteins other than Gsα, indicates that dopamine can transduce varied signaling responses upon the simultaneous stimulation of both these receptors. 相似文献
17.
Francesco Moccia Carlo Di Cristo William Winlow Anna Di Cosmo 《Invertebrate neuroscience : IN》2009,9(1):29-41
To examine the neurochemistry underlying the firing of the RPeD1 neuron in the respiratory central pattern generator of the
pond snail, Lymnaea stagnalis, we examined electrophysiologically and pharmacologically either “active” or “silent” preparations by intracellular recording
and pharmacology. GABA inhibited electrical firing by hyperpolarizing RPeD1, while picrotoxin, an antagonist of GABAA receptors, excited silent cells and reversed GABA-induced inhibition. Action potential activity was terminated by 1 mM glutamate
(Glu) while silent cells were depolarized by the GluR agonists, AMPA, and NMDA. Kainate exerted a complex triphasic effect
on membrane potential. However, only bath application of AMPA desensitized the firing. These data indicate that GABA inhibits
RPeD1 via activation of GABAA receptors, while Glu stimulates the neuron by activating AMPA-sensitive GluRs. 相似文献
18.
19.
The 126Gln of human interleukin-2 (IL-2) is a conserved amino acid residue. After substitution of 126Gln with Asp, the binding
abilities of this mutant to different composites of IL-2 receptor (R) subunits have been determined. Results show that 126AspIL-2
has higher affinity to IL-2R α β γ complex and normal affinity to IL-2R α β complex, but loses its binding ability to IL-2R
β γ complex, demonstrating that the 126Gln is the residue of human IL-2 which binds to IL-2R γ subunit.
Project supported by the “863” Project of China. 相似文献
20.
Khakpay R Polster D Köles L Skorinkin A Szabo B Wirkner K Illes P 《Purinergic signalling》2010,6(3):349-359
Locus coeruleus (LC) neurons in a rat brain slice preparation were superfused with a Mg2+-free and bicuculline-containing external medium. Under these conditions, glutamatergic spontaneous excitatory postsynaptic
currents (sEPSCs) were recorded by means of the whole-cell patch-clamp method. ATP, as well as its structural analogue 2-methylthio
ATP (2-MeSATP), both caused transient inward currents, which were outlasted by an increase in the frequency but not the amplitude
of the sEPSCs. PPADS, but not suramin or reactive blue 2 counteracted both effects of 2-MeSATP. By contrast, α,β-methylene
ATP (α,β-meATP), UTP and BzATP did not cause an inward current response. Of these latter agonists, only BzATP slightly facilitated
the sEPSC amplitude and strongly potentiated its frequency. PPADS and Brilliant Blue G, as well as fluorocitric acid and aminoadipic
acid prevented the activity of BzATP. Furthermore, BzATP caused a similar facilitation of the miniature (m)EPSC (recorded
in the presence of tetrodotoxin) and sEPSC frequencies (recorded in its absence). Eventually, capsaicin augmented the frequency
of the sEPSCs in a capsazepine-, but not PPADS-antagonizable, manner. In conclusion, the stimulation of astrocytic P2X7 receptors
appears to lead to the outflow of a signalling molecule, which presynaptically increases the spontaneous release of glutamate
onto LC neurons from their afferent fibre tracts. It is suggested, that the two algogenic compounds ATP and capsaicin utilise
separate receptor systems to potentiate the release of glutamate and in consequence to increase the excitability of LC neurons. 相似文献