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1.
The tachykinins substance P and neurokinin A participate in the regulation of gastrointestinal motility, secretion, vascular permeability and pain sensitivity. Advances made during the past two years corroborate a causal involvement of tachykinins in inflammation-induced disturbances of gut function, such as dysmotility, secretory diarrhoea, oedema and hyperalgesia. It would therefore appear that tachykinin receptors, which in the digestive system are expressed in a cell-specific manner, represent attractive targets for novel therapeutics in gastroenterology. 相似文献
2.
Holzer-Petsche U. Schimek E. Amann R. Lembeck F. 《Naunyn-Schmiedeberg's archives of pharmacology》1985,330(2):130-135
Summary Recently, two kassinin-like tachykinins have been isolated from mammalian nervous tissue. The potencies of these peptides, substance K (neurokinin ) and neuromedin K (neurokinin ) were compared with those of substance P, eledoisin, and kassinin in various pharmacological systems in vivo and in vitro.In contracting the isolated guinea-pig ileum and rabbit jejunum the potencies of eledoisin, kassinin, substance K, and neuromedin K were 13–80% that of substance P. In the rat vas deferens substance K and neuromedin K potentiated the electrically induced contractions with potencies similar to those of eledoisin and kassinin; they were 46–236 times as potent as substance P.In stimulating salivation in the rat after intravenous injection, eledoisin, kassinin, and substance K were respectively 2.3, 1.3 and 0.33 times as potent as substance P. In contrast, neuromedin K exhibited negligible activity. Each peptide tested led to a short fall in blood pressure after intravenous injection in the rabbit, substance P being 12–250 times as potent as the other peptides. Substance P was 20 times as potent as substance K or neuromedin K in inducing vasodilatation in the rat hind paw in vivo.Of the peptides tested, only substance P (10 nmol/min) significantly increased the release of histamine from the rat isolated hindquarter preparation.The results are discussed with respect to several theories of tachykinin receptor heterogeneity.The work was supported by the Austrian Scientific Research Funds, grant No. P5616, by the Austrian National Bank, grant No. 2216, and the Pain Research Commission of the Austrian Academy of Sciences 相似文献
3.
We review the actions of mammalian tachykinins on uterine smooth muscle. Derived from sensory neurones and non-neuronal cells within the female reproductive tract, tachykinins are potent uterotonic agents. Three tachykinin receptor genes, and the gene encoding neprilysin, the enzyme that inactivates tachykinins, are present in rat, mouse and human myometrium. In rat and human, the tachykinin NK2 receptor is important in mediating the uterotonic effects of tachykinins; actions at this receptor remain relatively stable or vary only slightly in the face of changing hormonal and gestational status. In contrast, ovarian steroids and pregnancy regulate expression of the tachykinin NK3, and to a lesser extent, the tachykinin NK1 receptor, as well as the activity of neprilysin. In the oestrogen primed mouse uterus, the tachykinin NK1 receptor primarily mediates tachykinin uterotonic effects, but there is a switch to the tachykinin NK2 receptor by late pregnancy. The possible physiological and pathological roles of tachykinins, including hemokinins and endokinins, in normal and premature labour, stress-induced abortion and menstrual disorders are briefly discussed. 相似文献
4.
In this study, we have used radioligand binding and functional techniques to investigate tachykinin receptors in the small
intestine of the cane toad Bufo marinus. The radioligand [125I]Bolton-Hunter [Sar9,Met(O2)11]substance P (selective at mammalian NK-1 receptors) showed no specific binding. Specific binding of [125I]Bolton-Hunter substance P ([125I]BHSP) was saturable, of high affinity (Kd 0.3 nM) and was inhibited by SP (IC50 0.64 nM) > ranakinin < neurokinin A (NKA) $ SP(5–11) $ neuropeptide γ $ scyliorhinin II > scyliorhinin I $ [Sar9]-SP $ neurokinin B < physalaemin < carassin >> SP(7–11) < eledoisin $ SP(4–11) < SP(6–11). Binding was also inhibited by
Gpp[NH]p $ GTPγS > App[NH]p, indicating a G-protein coupled receptor. The order of potency of tachykinins and analogues in
contracting the isolated lower small intestine was carassin (EC50 1.4 nM) > eledoisin < SP $ physalaemin $ ranakinin > SP(6–11) > scyliorhinin II $ neuropeptide γ > neurokinin B < NKA < scyliorhinin
I $ SP(4–11) $ SP(5–11) > [Sar9]SP > SP(7–11). In both studies, the selective mammalian NK-1, NK-2 and NK-3 receptor agonists [Sar9,Met(O2)11]SP, [Lys5,MeLeu9,Nle10]NKA(4–10) and senktide were weak or ineffective. There was a strong positive correlation between the pD2 and pIC50 values for mammalian tachykinins and analogues (r=0.907), but not for the non-mammalian tachykinins, which were all full agonists but variable binding competitors. [Sar9,Met(O2)11]-SP(pD2 5.7) was approximately 25-fold less potent as an agonist than [Sar9]SP, which was itself 25-fold weaker than SP. Responses to SP were significantly reduced (n = 8, P<0.001) by the antagonist [D-Arg1,D-Trp7,9,Leu11]-SP (spantide; 1 μM). Highly selective NK-1 receptor antagonists including CP 99994 and GR 82334 (both 1 μM) were ineffective
in both functional and binding studies. Tetrodotoxin (1 μM) did not inhibit contractile responses to SP, NKA and senktide.
In summary, this study has shown the presence of one or more tachykinin receptor in the toad intestine. The binding site recognised
by [125I]BHSP prefers SP and ranakinin. This toad “NK-1-like receptor” differs from the mammalian NK-1 receptor in having a low affinity
for all mammalian NK-1 selective ligands, including antagonists. For some non-mammalian peptides, their high potency as contractile
agonists relative to their poor binding affinity suggests the existence of other tachykinin receptors in the toad small intestine.
Received: 2 September 1997 / Accepted: 26 March 1998 相似文献
5.
Johansson A Liu L Holmgren S Burcher E 《Naunyn-Schmiedeberg's archives of pharmacology》2004,370(1):35-45
Two tachykinin peptides, bufokinin and Xenopus neurokinin A (X-NKA) were recently isolated from Xenopus laevis. In this study we investigated the tachykinin receptors in the Xenopus gastrointestinal tract. In functional studies using stomach circular muscle strips, all peptides had similar potencies (EC50 values 1–7 nM). The rank order of potency to contract the intestine was physalaemin (EC50 1 nM)bufokinin (EC50 3 nM)>substance P (SP)cod SP>NKA>>X-NKA (EC50 1,900 nM). No maximum response could be obtained for [Sar9,Met(O2)11]SP, eledoisin and kassinin. In stomach strips, the mammalian tachykinin receptor antagonists RP 67580 (NK1) and MEN 10376 (NK2) had agonistic effects but did not antagonize bufokinin or X-NKA. In intestinal strips, RP 67580 (1 M) reduced the maximal response to X-NKA but not bufokinin, while MEN 10376 was ineffective. [125I]BH-bufokinin bound with high affinity to a single class of sites, of KD 213±35 (stomach) and 172±9.3 pM (intestine). Specific binding of [125I]BH-bufokinin was displaced by bufokininSP>NKAeledoisinkassinin>X-NKA, indicating binding to a tachykinin NK1-like receptor. Selective tachykinin receptor antagonists were weak or ineffective. Other iodinated tachykinins ([125I]NKA and [125I]BH-eledoisin) displayed biphasic competition profiles, with the majority of sites preferring bufokinin rather than X-NKA. In conclusion, there is evidence for two different tachykinin receptors in Xenopus gastrointestinal tract. Both receptors may exist in stomach, whereas the bufokinin-preferring NK1-like receptor predominates in longitudinal muscle of the small intestine. Antagonists appear to interact differently with amphibian receptors, compared with mammalian receptors.Abbreviations Buf Bufokinin - cSP Cod SP - Ele Eledoisin - Kass Kassinin - NKA Neurokinin A - Phys Physalaemin - Sar9 [Sar9,Met(O2)11]SP - SP Substance P 相似文献
6.
Summary This study was an investigation of the effects of the tachykinin antagonists, spantide and (d-Pro4, d-Trp7, 9, 10)substance P 4-11, injected intracerebroventricularly (ICV), on the locomotor and behavioural responses of guinea-pigs to substance P (SP) injected ICV and to naloxone-induced morphine withdrawal. SP, 50 nmol, produced increased locomotor activity and behaviour that mimicked the response induced by injection of naloxone hydrochloride, 15 mg/kg, in guinea-pigs treated 2 h previously with morphine sulphate, 15 mg/kg. Spantide or (d-Pro4, d-Trp7, 9, 10)SP4-11, 10 nmol, reduced the locomotor and behavioural responses to SP and to morphine withdrawal. The results support the suggestion that SP or a related tachykinin might be a mediator of the opioid withdrawal response in the central nervous system as has been proposed for the enteric nervous system. 相似文献
7.
Microdialysis combined with radioimmunoassay was used to measure the release of neurokinin A-like immunoreactivity (NKA-LI) in the rat brain in vivo. The effect of a single dose of amphetamine (2 mg/kg s.c.) on the basal overflow and the potassium-induced release of NKA-LI was assessed in the nucleus accumbens and caudate-putamen. Amphetamine potentiated the potassum-stimulated release of NKA-LI by 71% in the nucleus accumbens, while no significant change was observed in the caudate-putamen. Amphetamine did not affect the basal NKA-LI overflow. 相似文献
8.
Helen M. Cox Iain R. Tough Kathryn Grayson Simon Yarrow 《Naunyn-Schmiedeberg's archives of pharmacology》1993,348(2):172-177
Summary Substance P(SP), neurokinin A (NKA), neurokinin B (NKB), [Sar9, Met (O2)11]-SP (SMSP), senktide, [Ala8]-NKA(4–10) and neuropeptide (NP) all stimulate secretory responses in rat descending colon mucosa under voltage clamp conditions. Secretory responses (measured as short circuit current under voltage clamp conditions) were transient and those evoked by SP, SMSP, NKA and senktide were significantly reduced by pretreating tissues with the chloride channel blocker, diphenylamine carboxylate (DPC). Concentration-response curves showed varying degrees of sensitivity to tetrodotoxin (TTX). Senktide-induced secretion was virtually abolished by TTX, while NP and [Ala8]-NKA(4–10) were not significantly altered. Rightward shifts of concentration-response curves were observed for SMSP, NKA and SP in TTX treated preparations compared with controls. NKA response curves in the presence of TTX were further inhibited by MEN10,207 and CP-96,345. GR71251, GR82334 and CP-96,345 all inhibited SMSP secretory responses with pA2 values of 5.8, 6.5 and 6.9 respectively. In conclusion three types of neurokinin receptor exist in preparations of rat colon mucosa and their relative location within neuronal and epithelial surfaces are discussed.
Correspondence to H. M. Cox at the above addressK. G. and S. Y. were project students with H. M. C. in the Department of Pharmacology, University of Cambridge. S. Y. was also a Wellcome Trust Vacation Scholar 相似文献
9.
A. R. Renzetti M. Criscuoli C. A. Maggi 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(1):139-144
The tachykinin NK2 receptors present in membranes of rat small intestine were characterized by means of tachykinin receptor agonists and antagonists,
by using the natural agonist, NKA, or the nonpeptide antagonist SR 48968, as radioligands.
The affinity of the antagonists was independent of the radioligand used, whereas the NK2 receptor selective agonists showed a different binding profile according to the radioligand. In particular, when using [125I]NKA, NKA and NKA(4–10) bound to a high affinity site, whilst [β-Ala8]NKA(4–10) and GR 64349 bound to a high and a low affinity site; the high affinity site was still detected in the presence of 100μM
GppNHp which produced a strong inhibition of the specific binding of [125I]NKA. On the other hand, when using [3H]SR 48968, NKA bound to a high affinity site, [β-Ala8]NKA(4–10) bound to a low affinity site and NKA(4–10) and GR 64349 bound to a high and a low affinity site; in this case, the high affinity site was no longer detected in the
presence of 1μM GppNHp, which did not reduce the specific binding of [3H]SR 48968 to NK2 receptors.
We interpreted these data as an indication that in the rat small intestine membranes [125I]NKA labels multiple conformations of G protein-coupled NK2 receptor which are distinguished by the use of selective receptor agonists, but not by peptide or nonpeptide antagonists.
Received: 11 September 1996 / Accepted: 12 March 1997 相似文献
10.
11.
M. Tramontana Riccardo Patacchini Alessandro Lecci Sandro Giuliani Carlo Alberto Maggi 《Naunyn-Schmiedeberg's archives of pharmacology》1998,358(3):293-300
We have characterized the contractile responses produced by stimulation of the tachykinin NK2 receptor in the hamster urinary bladder in vitro and in vivo. In isolated bladder strips, neurokinin A (NKA, pD
2 7.40, Emax 71% of the response to 80 mM KCl) and the synthetic tachykinin NK2 receptor selective agonist [βAla8]NKA(4–10) (pD
2 7.48, Emax 77% of the response to KCl) both induced a concentration-dependent contraction, whereas the tachykinin NK1 and NK3 receptor selective agonists, [Sar9]substance P sulfone and senktide, respectively, produced a negligible contractile effect. The bicyclic peptide antagonists
MEN 11420 and MEN 10627 behaved as competitive antagonists of the response to [βAla8]NKA(4–10) with apparent pK
B values of 9.3 and 9.7, respectively. Comparable apparent pK
B values were estimated against NKA (pK
B 9.2 and 9.4 for MEN 11420 and MEN 10627, respectively). Under isovolumetric recording of the intravesical pressure, the nicotinic
receptor agonist DMPP (0.6 μmol/kg i.v.) produced a phasic contraction of the hamster bladder in vivo that was abolished by
hexamethonium (110 μmol/kg i.v.) or by surgical ablation of pelvic ganglia. In vivo [βAla8]NKA(4–10) (10 nmol/kg i.v.) induced a tonic-type sustained bladder contraction with superimposed high frequency and small
amplitude (<12 mmHg) phasic contractions and, in about 70% of cases examined, a few high amplitude (>20 mmHg) phasic contractions.
Hexamethonium abolished the high amplitude phasic contractions, indicating their reflex origin. In animals subjected to the
ablation of pelvic ganglia, the urinary bladder response to [βAla8]NKA(4–10) was comparable to that observed after administration of hexamethonium. Moreover, hexamethonium did not affect the
contractile responses to [βAla8]NKA(4–10) in ganglionectomized animals. MEN 10627 and MEN 11420 produced a dose-dependent and long-lasting inhibition of
the contractile response to [βAla8]NKA(4–10): the least effective doses of the two antagonists were 30 and 3 nmol/kg i.v. for MEN 10627 and MEN 11420, respectively.
An almost complete and long-lasting inhibition of the response to the agonist was produced at doses of 10 and 100 nmol/kg
i.v. of MEN 11420 and MEN 10627. In urethane-anaesthetized hamsters the non-stop intravesical infusion of saline (50 μl/min)
produced repetitive micturition cycles which were abolished by hexamethonium (110 μmol/kg i.v.) or by surgical removal of
the pelvic ganglia. MEN 11420 (100 nmol/kg) had no significant effect on the volume-evoked micturition reflex in anaesthetized
hamsters. In conclusion, the hamster urinary bladder is a suitable preparation for studying the action of tachykinin NK2 receptor antagonists in vivo: in this species, the stimulation of tachykinin NK2 receptors induces bladder contractions. Blockade of tachykinin NK2 receptors does not appreciably modify the volume-evoked micturition reflex in this species.
Received: 22 April 1998 / Accepted: 12 June 1998 相似文献
12.
13.
Synergistic role of muscarinic acetylcholine and tachykinin NK-2 receptors in intestinal peristalsis
It is known that tachykinins (substance P, neurokinin A) participate in the excitatory neural pathways subserving peristaltic motor activity in the intestine. The aim of the present study was to elucidate the types of tachykinin receptor (NK-1 or NK-2) involved in peristalsis by the use of receptor subtype-selective antagonists. Peristaltic motility in isolated segments of the guinea-pig ileum was induced by pumping fluid into the oral end of the intestinal segment. By way of the intraluminal pressure the compliance of the intestinal wall during the preparatory phase and the pressure threshold to trigger the emptying phase of peristalsis were recorded. The tachykinin antagonists were used at concentrations that were at least 30 times in excess of the equilibrium dissociation constants which had previously been evaluated with receptor subtype-selective agonists on the guineapig ileum circular muscle. The NK-1 selective antagonist CP-96,345 (0.3 M) had a slight stimulant influence on peristalsis, whereas the NK-2 selective antagonists MEN-10,376 (10 M), GR-94,800 (0.3 M) and SR-48,968 (0.1 M) led to a small inhibition of motor activity. However, when given after exposure of the ileum to a threshold concentration of atropine (5–20 nM) causing little depression of peristalsis, the tachykinin NK-2 receptor antagonists invariably abolished peristalsis. This synergistic interaction was not seen when SR-48,968 was administered after the ileal segments had been exposed to concentrations of hexamethonium, isoproterenol or calcitonin gene-related peptide that by themselves caused a slight inhibition of peristalsis only. CP-96,345 was without effect on peristalsis when it was applied in the presence of a threshold concentration of atropine. These findings indicate that transmission via tachykinin NK-2, but not NK-1, receptors synergizes with cholinergic transmission via muscarinic receptors in the relay of excitatory enteric pathways subserving intestinal peristalsis.
Correspondence to: P. Holzer at the above address 相似文献
14.
A. Lecci Sandro Giuliani Manuela Tramontana Marco Criscuoli Carlo Alberto Maggi 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(2):182-188
This study investigates the role of tachykinin NK1 and NK2 receptors in motor responses induced by the intravesical instillation of capsaicin in urethane-anaesthetized rats. SR 140,333
(1 μmol/kg, i.v.), a non-peptide NK1 receptor antagonist, abolished urinary bladder contractions induced by the selective NK1 receptor agonist [Sar9]SP-sulfone (0.1-100 nmol/kg, i.v.) without affecting those induced by the NK2 receptor agonist [?Ala8]NKA(4-10). MEN 11,420 (100 nmol/kg, i.v.), a cyclic peptide NK2 receptor antagonist, abolished bladder contractions induced by [?Ala8]NKA(4-10) (0.3-300 nmol/kg, i.v.) without modifying those induced by [Sar9]SP-sulfone. Intravesical instillation of capsaicin (6 nmol/0.6 ml/rat) produced a motor response consisting in a primary
contraction followed by a series of high amplitude phasic contractions. The intravesical instillation of saline (0.6 ml/rat)
produced a primary contraction of lower amplitude with respect to that induced by capsaicin and the total area under the curve
was also lower in saline-instilled rats, however the number and the amplitude of phasic contractions was similar to that induced
by capsaicin. MEN 11,420 (100 nmol/kg, i.v.) did not modify motor responses induced by the intravesical administration of
saline. In contrast, in capsaicin-instilled rats, MEN 11,420 (100 nmol/kg, i.v.) reduced the primary contraction, the area
under the curve and also the number of phasic contractions. SR 140,333 (1 μmol/kg, i.v.) reduced the primary contraction but
not other parameters. The combination of SR 140,333 (1 μmol/kg, i.v.) and MEN 11,420 (100 nmol/kg, i.v.) produced an additive
inhibitory effect on the primary contraction but not a further inhibition on other parameters with respect to that observed
with MEN 11,420 alone. In hexamethonium (110 μmol/kg, i.v.)-pretreated animals the intravesical instillation of capsaicin
produced a tonic contraction having greater amplitude and area than that induced by saline. MEN 11,420, but not SR 140,333,
significantly reduced the bladder response to capsaicin in hexamethonium-pretreated rats. Again, the combined administration
of MEN 11,420 and SR 140,333 did not produce further inhibitory effect in comparison to MEN 11,420 alone. It is concluded
that the motor responses induced by the intravesical instillation of capsaicin are mediated by the activation of peripheral
tachykinin NK2 receptors.
Received: 11 February 1997 / Accepted: 17 April 1997 相似文献
15.
Franco Luzzani Domenico Barone Giulio Galliani Alfredo Glässer 《European journal of pharmacology》1983,87(1):61-66
The interaction of glucocorticoids with thymic cytosol receptors in the adrenalectomized rat was studied by a method based on their capacity to deplete cytosol receptors when administered in vivo. Three h after a single oral administration of reference steroids at various dose levels, thymus cytosol aliquots were incubated with a saturating concentration of [3H]dexamethasome (30 nM) for 24 h at 0–2°C with and without 2 000 nM unlabeled dexamethasone. Bound radioactivity was determined by dextran-coated charcoal adsorption. The depletion of cytosol receptors was dose-dependent for each glucocorticoid, with the following ED50 (mg/kg): fluocinolone acetonide 0.032, dexamethasone 17.0. A striking correlation (r 0.991) between ex vivo receptor binding and thymolytic effect was observed. When data from in vitro competition studies were compared with those obtained in ex vivo experiments, the latter were correlated more tightly with the biological response. 相似文献
16.
Paul Fosbraey Roland L. Featherstone Ian K. M. Morton 《Naunyn-Schmiedeberg's archives of pharmacology》1984,326(2):111-115
Summary A range of tachykinins including substance P were studied for their ability to contract the guinea-pig ileum longitudinal muscle preparation on brief exposure (20 s) to the peptides, and their ability to evoke the release of [3H]-acetylcholine (ACh) from previously labelled stores within the myenteric plexus. With respect to their immediate spasmogenic activity, none of the peptides differed greatly in potency from substance P. Atropine did not modify the response to the tachykinins suggesting that the release of ACh does not contribute to the contraction resulting from brief exposure to the peptides. In the release studies, all tachykinins used produced a dose-related, calcium-dependent release of [3H]-ACh but the differences in potency were much greater. Eledoisin was the most potent and its evoked release of ACh was unaffected by hyoscine, hexamethonium, guanethidine and naloxone suggesting the release is not mediated via, or modulated by, opiate or autonomic neuronal influences. The two orders of tachykinin potency found suggest that the two processes, initial contraction and ACh release, may be principally mediated via two distinct subclasses of substance P receptor designated SP-P and SP-E respectively. 相似文献
17.
H. Kuwahara T. Sakurada S. Sakurada A. Yonezawa R. Ando K. Kisara F. Osakada E. Munekata 《Naunyn-Schmiedeberg's archives of pharmacology》1987,336(6):656-660
Summary The effect of unilateral sciatic nerve transection on behavioural responses produced by intrathecal administration of substance P (SP), neurokinin A, eledoisin and physalaemin was investigated in the rat. The injection of SP (3 nmol/rat) into the subarachnoid space was followed by reciprocal scratching, biting and licking of the fore- and hind-limbs. There was no observable difference in the behavioural response to SP between rats with nerve transection and sham operated rats at 5 days after operation. Whereas at 10, 20, and 30 days after nerve transection the response to SP was significantly increased as compared with sham operated rats. This phenomenon was also observed with neurokinin A (1.5, 3.0 and 6.0 nmol/rat), eledoisin (0.05 and 0.10 nmol/rat) and physalaemin (0.05 and 0.10 nmol/ rat) at 10 days after operation. Ipsilateral depletion of SP from the lumbar (L4-L6) spinal cord was observed at 5, 10, 20, and 30 days after the unilateral transection of the sciatic nerve. These results suggest that sciatic nerve transection may produce an increased response to tachykinins through an enhanced sensitivity of tachykinin receptors in the lumbar cord.
Send offprint requests to T. Sakurada 相似文献
18.
Wijkhuisen A Tymciu S Fischer J Alexandrenne C Créminon C Frobert Y Grassi J Boquet D Conrath M Couraud JY 《European journal of pharmacology》2003,468(3):175-182
Two peptides were derived from the structural analysis of a previously described monoclonal antibody [Mol. Immunol. 37 (2000) 423] against the tachykinin NK(1) receptor for the neuropeptide substance P. Here we show that these two peptides were able to inhibit the inositol phosphate transduction pathway triggered both by substance P and neurokinin A, another high-affinity endogenous ligand for the tachykinin NK(1) receptor. They also reduced the cAMP production induced by substance P. By contrast, only one antagonist peptide was able to prevent substance P and neurokinin A from binding the receptor, as revealed both by biochemical and autoradiographic studies. First, these results illustrate the generality of the antibody-based strategy for developing new bioactive peptides. Second, they indicate that antagonists, even exhibiting very close amino acid composition, can interact with the tachykinin NK(1) receptor at different contact sites, some of them clearly distinct from the contact domains for endogenous agonists. 相似文献
19.
INTRODUCTION Almost 50 % of cells in central nervous systemare astrocytes. They play an important role in normalphysiological activity andhave intimate relationship withneurons. There is a close bidirectional communicationexisting between neurons and astrocytes[1]. Glutamate,as the most important excitatory transmitter in centralnervous system, is proved to be a crucial bridge be-tween astrocytes and neurons. Astrocytes respondedto glutamate released from neurons by intracellular C… 相似文献