(3.235.108.188) 您好!臺灣時間:2021/03/07 20:25
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:李孟娟
研究生(外文):Meng-Jiyuan Li
論文名稱:大鼠A7核區正腎上腺素神經元之膽鹼性調控機制
論文名稱(外文):Cholinergic Modulation in A7 Noradrenergic Neurons in Rats
指導教授:閔明源
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:動物學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:英文
論文頁數:56
中文關鍵詞:腦幹A7核區全細胞電生理記錄乙醯膽鹼蕈毒膽鹼性受器TRP通道腳橋被蓋核痛覺傳導
外文關鍵詞:brainstemA7 cell groupwhole-cell recordingAChmAChRTRP channelsPPTgsynaptic transmission
相關次數:
  • 被引用被引用:0
  • 點閱點閱:247
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
乙醯膽鹼(acetylcholine, ACh)對於痛覺的調控有重要的功能。文獻指出乙醯膽鹼能引起鎮痛效果(analgesia),且在脊髓中,乙醯膽鹼或其他膽鹼性促效劑(cholinergic agonists)參與了由α2正腎上腺素受體(α2-adrenergic receptor)調控之止痛功能。行為實驗也提出正腎上腺素之下行性痛覺調控路徑(NAergic descending pain modulation pathway)與蕈毒膽鹼性系統(muscarinic cholinergic system)在腦內有交互作用的可能性。然而,目前並無直接的證據支持此項論述。本研究利用碳醯膽鹼素(carbachol, CCh)這類不易被乙醯膽鹼水解酵素(cholinesterase)分解的膽鹼性促效劑,檢視其對於腦幹中分泌正腎上腺素之A7兒茶酚胺細胞群(catecholamine cell group)的影響。文獻已證實位於腦幹的A7兒茶酚胺細胞群會投射其軸突至脊髓背角(dorsal horn),分泌正腎上腺素並進行痛覺訊息傳遞的調控。在此實驗中,我們對幼鼠腦幹薄片中的A7細胞進行全細胞記錄(whole-cell recording),當膜電位被箝定在-70 mV時,碳醯膽鹼素可於A7細胞上引發一內流電流,且可被蕈毒膽鹼性受器拮抗劑─阿托品(atropine)抑制。利用喜八辛(himbacine)在不同濃度下可抑制不同亞型之蕈毒膽鹼性受器的特性,發現此電流應是活化類M1亞型受器而引發,且G-protein以及磷脂酶C(phospholipase C)的活化並非參與此電流的主要分子機制。另外,此電流的反轉電位(reversal potential)約為-12.6 mV,並在NMDG取代胞外鈉離子時被減弱,顯示可能開啟了非專一性陽離子通道(nonselective cation channel),如Transient Receptor Potential通道(TRP channels)。實驗結果顯示在三種TRP通道抑制劑(2APB, SKF96365, ruthenium red)下,碳醯膽鹼素的反應皆會被顯著抑制。
藉由電刺激腳橋被蓋核(pedunculopontine tegmental nucleus, PPTg),可於A7正腎上腺素細胞中引發一可被阿托品部分抑制的突觸後興奮性電流(excitatory postsynaptic currents),顯示腳橋被蓋核的軸突有投射至A7核區,並可釋放乙醯膽鹼以增強A7細胞的興奮性。在此突觸連結上,也發現有自主回饋抑制(auto-inhibition)的調控現象。
綜合以上結果,此篇研究證實了蕈毒膽鹼性受器可透過開啟TRP通道調控A7正腎上腺素分泌細胞的活性,但並非主要經由活化G蛋白與磷脂酶C的胞內分子訊息傳遞路徑,且腳橋被蓋核可釋放內生性乙醯膽鹼至A7核區,影響A7細胞的活性。此外,更為脊髓以上蕈毒膽鹼性系統與正腎上腺素之下行性痛覺調控路徑的交互作用提供了有利的證據。


Acetylcholine (ACh) is one of principal neurotransmitters involved in pain modulation. Many behavioral studies have shown that central or peripheral ACh administrations can evoke analgesia, and have proved that cholinergic agonists can serve as a synergistic role of α2 adrenergic receptors-mediated antinociception in the spinal cord. Moreover, recent behavioral researches also indicate that there might be supraspinal interactions between muscarinic cholinergic system and noradrenergic (NAergic) pain descending pathway. Nevertheless, there is currently no direct evidence to support this argument. In this study, we investigated the effect of carbachol (CCh), a cholinergic agonist, on NAergic neurons of A7 catecholamine cell group, which projects NAergic fibers to the dorsal horn of the spinal cord to modulate nociceptive signaling. Whole-cell recordings were made from A7 neurons in voltage-clamp mode with membrane voltage clamped at -70 mV in brainstem slices taken from rat pups. Bath application of 25 μM CCh evoked inward currents, which were blocked by 1.5 μM atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, suggesting that carbachol-induced currents (ICCh) were mediated through mAChR. Furthermore, ICCh were significantly attenuated with the existence of high concentration of himbacine, a dose-selective antagonist of mAChRs, showing that mAChRs on NAergic A7 neurons activated by CCh were M1-like mAChRs. Surprisingly, the ICCh were not blocked with internal administration of GDP-β-S, a non-catalytic analogue of GDP, suggesting that the ICCh were G-protein-independent. Bath application of U73122, a phospholipase C inhibitor, slightly but significantly blocked the ICCh, showing that phospholipase C was not the major participant in ICCh. The ICCh were reversed at about -12.6 mV and blocked by extracellular application of NMDG substituted for Na+, showing that ICCh were caused through opening a nonselective cation channel, presumably by transient receptor potential (TRP) channels. Indeed, ICCh were significantly attenuated by several antagonists of TRP channels, including 2APB, SKF96365 and ruthenium red. Besides, high frequency stimulation at pedunculopontine tegmental nucleus (PPTg) evoked an inward current partially blocked by atropine, suggesting PPTg projected their axons to NAergic A7 neurons. There was an auto-inhibition in PPTg-A7 synaptic transmission.
These results indicate that mAChR modulate the NAergic A7 neurons via activating TRP channels without the requirement of G-protein and phospholipase C, and there is endogenous ACh released from PPTg onto NAergic A7 neurons. The above results provide an evidence of supraspinal interaction between muscarinic cholinergic system and NAergic descending pain pathway.


CONTENTS
致謝………………………………………………………………………i
摘要……………………………………………………………………iii
ABASTRACT…………………………………………………………………v
INTRODUCTION……………………………………………………………1
Noradrenergic (NAergic) system in the central nervous system.....................................................1
A7 catecholamine cell group and descending pain modulation pathway....................................................2
The cholinergic system in the brain......................................................4
Cellular response to activation of muscarinic acetylcholine receptors (mAChRs).........................................5
The role of cholinergic mechanism in pain modulation………………………………………………………………6
Aim of the study………………………………………………………7
MATERIALS AND METHODS…………………………………………………8
Preparation of brain stem slices…………………………………8
Electrophysiology……………………………………………………..8
Measurement of liquid junction potentials……………………11
Drug………………………………………………………………………12
Filling recorded neurons with biocytin and immunohistochemistry…………………………………………………13
Statistic analysis……………………………………………………14
RESULTS…………………………………………………………………15
Identification of NAergic A7 cell groups in rat brainstem slices……………………………………………………………………15
CCh could increase the spontaneous firing rates of NAergic A7 neurons………………………………………………………………16
CCh could elicit an inward current on NAergic A7 neurons through muscarinic ACh receptors…………………………………16
mAChRs on NAergic A7 neurons activated by CCh were M1-like mAChRs……………………………………………………………………18
G-protein and phospholipase C (PLC) were not the major participants in CCh-induced currents......................19
CCh-induced currents might be contributed by mixed cation flux………………………………………………………………………20
CCh might activate TRP-like channels on NAergic A7 neurons…………………………………………………………………21
Pedunculopontine tegmental nucleus (PPTg) projects their axons to A7 NAergic neurons………………………………………22
There is an auto-inhibition in PPTg-A7 synaptic transmission……………………………………………………………23
DISCUSSION………………………………………………………………25
mAChR plays an important role in cholinergic modulation on A7 NAergic neurons……………………………………………………26
M1-like mAChRs are expressed on NAergic A7 neurons…………………………………………………………………27
mAChRs on NAergic A7 neurons are couple to TRP-like channels…………………………………………………………………28
mAChRs on NAergic A7 neurons are G-protein-independent……………………………………………………………29
Pedunculopontine tegmental nucleus (PPTg) projects their axons to A7 NAergic neurons………………………………………30
There is an auto-inhibition between PPTg-A7 synaptic transmissions…………………………………………………………32
Physiological implication for the action of ACh released from PPTg on A7 NAergic neurons…………………………………33
REFENRENCES……………………………………………………………35
FIGURES…………………………………………………………………44


REFERENCES
Aimone, L.D., Jones, S.L. & Gebhart, G.F. (1987) Stimulation-produced descending inhibition from the periaqueductal gray and nucleus raphe magnus in the rat: mediation by spinal monoamines but not opioids. Pain, 31, 123-136.

Aston-Jones, G. & Cohen, J.D. (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci, 28, 403-450.

Bajic, D., Van Bockstaele, E.J. & Proudfit, H.K. (2001) Ultrastructural analysis of ventrolateral periaqueductal gray projections to the A7 catecholamine cell group. Neuroscience, 104, 181-197.

Bengtson, C.P., Tozzi, A., Bernardi, G. & Mercuri, N.B. (2004) Transient receptor potential-like channels mediate metabotropic glutamate receptor EPSCs in rat dopamine neurones. J Physiol, 555, 323-330.

Bonner, T.I., Buckley, N.J., Young, A.C. & Brann, M.R. (1987) Identification of a family of muscarinic acetylcholine receptor genes. Science, 237, 527-532.

Burnett, A. & Gebhart, G.F. (1991) Characterization of descending modulation of nociception from the A5 cell group. Brain Res, 546, 271-281.

Caulfield, M.P. & Birdsall, N.J. (1998) International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev, 50, 279-290.

Clark, F.M. & Proudfit, H.K. (1991a) The projection of noradrenergic neurons in the A7 catecholamine cell group to the spinal cord in the rat demonstrated by anterograde tracing combined with immunocytochemistry. Brain Res, 547, 279-288.

Clark, F.M. & Proudfit, H.K. (1991b) Projections of neurons in the ventromedial medulla to pontine catecholamine cell groups involved in the modulation of nociception. Brain Res, 540, 105-115.

Dahlstrom, A. & Fuxe, K. (1964) Localization of monoamines in the lower brain stem. Experientia, 20, 398-399.

Danzebrink, R.M. & Gebhart, G.F. (1990) Antinociceptive effects of intrathecal adrenoceptor agonists in a rat model of visceral nociception. J Pharmacol Exp Ther, 253, 698-705.

Dias, Q.M., Crespilho, S.F., Silveira, J.W. & Prado, W.A. (2009) Muscarinic and alpha(1)-adrenergic mechanisms contribute to the spinal mediation of stimulation-induced antinociception from the pedunculopontine tegmental nucleus in the rat. Pharmacol Biochem Behav, 92, 488-494.

Dresviannikov, A.V., Bolton, T.B. & Zholos, A.V. (2006) Muscarinic receptor-activated cationic channels in murine ileal myocytes. Br J Pharmacol, 149, 179-187.

Duttaroy, A., Gomeza, J., Gan, J.W., Siddiqui, N., Basile, A.S., Harman, W.D., Smith, P.L., Felder, C.C., Levey, A.I. & Wess, J. (2002) Evaluation of muscarinic agonist-induced analgesia in muscarinic acetylcholine receptor knockout mice. Mol Pharmacol, 62, 1084-1093.

Egorov, A.V., Angelova, P.R., Heinemann, U. & Muller, W. (2003) Ca2+-independent muscarinic excitation of rat medial entorhinal cortex layer V neurons. Eur J Neurosci, 18, 3343-3351.

Egorov, A.V., Unsicker, K. & von Bohlen und Halbach, O. (2006) Muscarinic control of graded persistent activity in lateral amygdala neurons. Eur J Neurosci, 24, 3183-3194.

Eisenach, J.C. (1999) Muscarinic-mediated analgesia. Life Sci, 64, 549-554.

Evellin, S., Nolte, J., Tysack, K., vom Dorp, F., Thiel, M., Weernink, P.A., Jakobs, K.H., Webb, E.J., Lomasney, J.W. & Schmidt, M. (2002) Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine receptor mediated by cyclic AMP and the GTPase Rap2B. J Biol Chem, 277, 16805-16813.

Forster, G.L. & Blaha, C.D. (2003) Pedunculopontine tegmental stimulation evokes striatal dopamine efflux by activation of acetylcholine and glutamate receptors in the midbrain and pons of the rat. Eur J Neurosci, 17, 751-762.

Gee, C.E., Benquet, P. & Gerber, U. (2003) Group I metabotropic glutamate receptors activate a calcium-sensitive transient receptor potential-like conductance in rat hippocampus. J Physiol, 546, 655-664.

Graham, A., Court, J.A., Martin-Ruiz, C.M., Jaros, E., Perry, R., Volsen, S.G., Bose, S., Evans, N., Ince, P., Kuryatov, A., Lindstrom, J., Gotti, C. & Perry, E.K. (2002) Immunohistochemical localisation of nicotinic acetylcholine receptor subunits in human cerebellum. Neuroscience, 113, 493-507.

Guyenet, P.G. (1991) Chapter 28 Central noradrenergic neurons: the autonomic connection. In Barnes, C.D., Pompeiano, O. (eds) Progress in Brain Research. Elsevier, pp. 365-380.

Haj-Dahmane, S. & Andrade, R. (1996) Muscarinic activation of a voltage-dependent cation nonselective current in rat association cortex. J Neurosci, 16, 3848-3861.

Holden, J.E. & Proudfit, H.K. (1998) Enkephalin neurons that project to the A7 catecholamine cell group are located in nuclei that modulate nociception: ventromedial medulla. Neuroscience, 83, 929-947.

Holden, J.E., Schwartz, E.J. & Proudfit, H.K. (1999) Microinjection of morphine in the A7 catecholamine cell group produces opposing effects on nociception that are mediated by alpha1- and alpha2-adrenoceptors. Neuroscience, 91, 979-990.

Holden, J.E., Van Poppel, A.Y. & Thomas, S. (2002) Antinociception from lateral hypothalamic stimulation may be mediated by NK(1) receptors in the A7 catecholamine cell group in rat. Brain Res, 953, 195-204.

Honda, K., Horikawa, K., Ando, S., Koga, K., Kawata, S., Migita, K. & Takano, Y. (2008) The spinal muscarinic M(1) receptors and GABA(A) receptors contribute to the McN-A-343-induced antinociceptive effects during thermal stimulation of mice. J Pharmacol Sci, 108, 472-479.

Ishibashi, M., Leonard, C.S. & Kohlmeier, K.A. (2009) Nicotinic activation of laterodorsal tegmental neurons: implications for addiction to nicotine. Neuropsychopharmacology, 34, 2529-2547.

Iwamoto, E.T. (1989) Antinociception after nicotine administration into the mesopontine tegmentum of rats: evidence for muscarinic actions. J Pharmacol Exp Ther, 251, 412-421.

Iwamoto, E.T. & Marion, L. (1993) Adrenergic, serotonergic and cholinergic components of nicotinic antinociception in rats. J Pharmacol Exp Ther, 265, 777-789.

Jensen, T.S. & Yaksh, T.L. (1986) Examination of spinal monoamine receptors through which brainstem opiate-sensitive systems act in the rat. Brain Res, 363, 114-127.

Jeong, D.G., Park, W.K. & Park, S. (2008) Artemin activates axonal growth via SFK and ERK-dependent signalling pathways in mature dorsal root ganglia neurons. Cell Biochem Funct, 26, 210-220.

Katayama, Y., Watkins, L.R., Becker, D.P. & Hayes, R.L. (1984) Non-opiate analgesia induced by carbachol microinjection into the pontine parabrachial region of the cat. Brain Res, 296, 263-283.

Kender, R.G., Harte, S.E., Munn, E.M. & Borszcz, G.S. (2008) Affective analgesia following muscarinic activation of the ventral tegmental area in rats. J Pain, 9, 597-605.

Kubo, T., Fukuda, K., Mikami, A., Maeda, A., Takahashi, H., Mishina, M., Haga, T., Haga, K., Ichiyama, A., Kangawa, K. & et al. (1986a) Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor. Nature, 323, 411-416.

Kubo, T., Maeda, A., Sugimoto, K., Akiba, I., Mikami, A., Takahashi, H., Haga, T., Haga, K., Ichiyama, A., Kangawa, K. & et al. (1986b) Primary structure of porcine cardiac muscarinic acetylcholine receptor deduced from the cDNA sequence. FEBS Lett, 209, 367-372.

Kwiat, G.C. & Basbaum, A.I. (1992) The origin of brainstem noradrenergic and serotonergic projections to the spinal cord dorsal horn in the rat. Somatosens Mot Res, 9, 157-173.

Lavoie, B. & Parent, A. (1994) Pedunculopontine nucleus in the squirrel monkey: distribution of cholinergic and monoaminergic neurons in the mesopontine tegmentum with evidence for the presence of glutamate in cholinergic neurons. J Comp Neurol, 344, 190-209.

Lothe, A., Li, P., Tong, C., Yoon, Y., Bouaziz, H., Detweiler, D.J. & Eisenach, J.C. (1994) Spinal cholinergic alpha-2 adrenergic interactions in analgesia and hemodynamic control: role of muscarinic receptor subtypes and nitric oxide. J Pharmacol Exp Ther, 270, 1301-1306.

Lu, B., Su, Y., Das, S., Wang, H., Wang, Y., Liu, J. & Ren, D. (2009) Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80. Nature, 457, 741-744.

Ma, H.C., Dohi, S., Wang, Y.F., Ishizawa, Y. & Yanagidate, F. (2001) The antinociceptive and sedative effects of carbachol and oxycodone administered into brainstem pontine reticular formation and spinal subarachnoid space in rats. Anesth Analg, 92, 1307-1315.

Ma, L., Seager, M.A., Wittmann, M., Jacobson, M., Bickel, D., Burno, M., Jones, K., Graufelds, V.K., Xu, G., Pearson, M., McCampbell, A., Gaspar, R., Shughrue, P., Danziger, A., Regan, C., Flick, R., Pascarella, D., Garson, S., Doran, S., Kreatsoulas, C., Veng, L., Lindsley, C.W., Shipe, W., Kuduk, S., Sur, C., Kinney, G., Seabrook, G.R. & Ray, W.J. (2009) Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation. Proc Natl Acad Sci U S A, 106, 15950-15955.

May, L.G., Johnson, S., Krebs, S., Newman, A. & Aronstam, R.S. (1999) Involvement of protein kinase C and protein kinase A in the muscarinic receptor signalling pathways mediating phospholipase C activation, arachidonic acid release and calcium mobilisation. Cell Signal, 11, 179-187.

McCormick, D.A. & Prince, D.A. (1985) Two types of muscarinic response to acetylcholine in mammalian cortical neurons. Proc Natl Acad Sci U S A, 82, 6344-6348.

McCormick, D.A. & Prince, D.A. (1986) Acetylcholine induces burst firing in thalamic reticular neurones by activating a potassium conductance. Nature, 319, 402-405.

Mesulam, M.M., Mufson, E.J., Wainer, B.H. & Levey, A.I. (1983) Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1-Ch6). Neuroscience, 10, 1185-1201.

Millan, M.J. (2002) Descending control of pain. Prog Neurobiol, 66, 355-474.

Miller, J.H., Aagaard, P.J., Gibson, V.A. & McKinney, M. (1992) Binding and functional selectivity of himbacine for cloned and neuronal muscarinic receptors. J Pharmacol Exp Ther, 263, 663-667.

Min, M.Y., Hsu, P.C., Lu, H.W., Lin, C.J. & Yang, H.W. (2007) Postnatal development of noradrenergic terminals in the rat trigeminal motor nucleus: A light and electron microscopic immunocytochemical analysis. Anat Rec (Hoboken), 290, 96-107.

Min, M.Y., Wu, Y.W., Shih, P.Y., Lu, H.W., Lin, C.C., Wu, Y., Li, M.J. & Yang, H.W. (2008) Physiological and morphological properties of, and effect of substance P on, neurons in the A7 catecholamine cell group in rats. Neuroscience, 153, 1020-1033.

Min, M.Y., Wu, Y.W., Shih, P.Y., Lu, H.W., Wu, Y., Hsu, C.L., Li, M.J. & Yang, H.W. (2010) Roles of A-type potassium currents in tuning spike frequency and integrating synaptic transmission in noradrenergic neurons of the A7 catecholamine cell group in rats. Neuroscience, 168, 633-645.

Neher, E. (1992) Correction for liquid junction potentials in patch clamp experiments. Methods Enzymol, 207, 123-131.

Park, J.H., Kim, S.K., Kim, H.N., Sun, B., Koo, S., Choi, S.M., Bae, H. & Min, B.I. (2009) Spinal cholinergic mechanism of the relieving effects of electroacupuncture on cold and warm allodynia in a rat model of neuropathic pain. J Physiol Sci, 59, 291-298.

Paxinos, G. & Watson, C. (2007) The rat brain in stereotaxic coordinates. Academic Press/Elsevier, Amsterdam ; Boston ;.

Peng, Y.B., Lin, Q. & Willis, W.D. (1996) Involvement of alpha-2 adrenoceptors in the periaqueductal gray-induced inhibition of dorsal horn cell activity in rats. J Pharmacol Exp Ther, 278, 125-135.

Pertovaara, A. (2006) Noradrenergic pain modulation. Prog Neurobiol, 80, 53-83.

Ramsey, I.S., Delling, M. & Clapham, D.E. (2006) An introduction to TRP channels. Annu Rev Physiol, 68, 619-647.

Rolland, J.F., Henquin, J.C. & Gilon, P. (2002) G protein-independent activation of an inward Na(+) current by muscarinic receptors in mouse pancreatic beta-cells. J Biol Chem, 277, 38373-38380.

Shirey, J.K., Brady, A.E., Jones, P.J., Davis, A.A., Bridges, T.M., Kennedy, J.P., Jadhav, S.B., Menon, U.N., Xiang, Z., Watson, M.L., Christian, E.P., Doherty, J.J., Quirk, M.C., Snyder, D.H., Lah, J.J., Levey, A.I., Nicolle, M.M., Lindsley, C.W. & Conn, P.J. (2009) A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning. J Neurosci, 29, 14271-14286.

Steckler, T., Inglis, W., Winn, P. & Sahgal, A. (1994) The pedunculopontine tegmental nucleus: a role in cognitive processes? Brain Res Brain Res Rev, 19, 298-318.

Swayne, L.A., Mezghrani, A., Varrault, A., Chemin, J., Bertrand, G., Dalle, S., Bourinet, E., Lory, P., Miller, R.J., Nargeot, J. & Monteil, A. (2009) The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic beta-cell line. EMBO Rep, 10, 873-880.

Takano, Y. & Yaksh, T.L. (1992) Characterization of the pharmacology of intrathecally administered alpha-2 agonists and antagonists in rats. J Pharmacol Exp Ther, 261, 764-772.

Takeda, D., Nakatsuka, T., Gu, J.G. & Yoshida, M. (2007) The activation of nicotinic acetylcholine receptors enhances the inhibitory synaptic transmission in the deep dorsal horn neurons of the adult rat spinal cord. Mol Pain, 3, 26.

Waelbroeck, M., Tastenoy, M., Camus, J. & Christophe, J. (1990) Binding of selective antagonists to four muscarinic receptors (M1 to M4) in rat forebrain. Mol Pharmacol, 38, 267-273.

Wess, J. (1996) Molecular biology of muscarinic acetylcholine receptors. Crit Rev Neurobiol, 10, 69-99.

Wess, J. (2003) Novel insights into muscarinic acetylcholine receptor function using gene targeting technology. Trends Pharmacol Sci, 24, 414-420.

Wess, J., Blin, N., Yun, J., Schoneberg, T. & Liu, J. (1996) Molecular aspects of muscarinic receptor assembly and function. Prog Brain Res, 109, 153-162.

Wess, J., Eglen, R.M. & Gautam, D. (2007) Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nat Rev Drug Discov, 6, 721-733.

Westlund, K.N. & Craig, A.D. (1996) Association of spinal lamina I projections with brainstem catecholamine neurons in the monkey. Exp Brain Res, 110, 151-162.

Winn, P. (2006) How best to consider the structure and function of the pedunculopontine tegmental nucleus: Evidence from animal studies. Journal of the Neurological Sciences, 248, 234-250.

Yang, W., Klaman, L.D., Chen, B., Araki, T., Harada, H., Thomas, S.M., George, E.L. & Neel, B.G. (2006) An Shp2/SFK/Ras/Erk signaling pathway controls trophoblast stem cell survival. Dev Cell, 10, 317-327.

Yeomans, D.C., Clark, F.M., Paice, J.A. & Proudfit, H.K. (1992) Antinociception induced by electrical stimulation of spinally projecting noradrenergic neurons in the A7 catecholamine cell group of the rat. Pain, 48, 449-461.

Yeomans, D.C. & Proudfit, H.K. (1990) Projections of substance P-immunoreactive neurons located in the ventromedial medulla to the A7 noradrenergic nucleus of the rat demonstrated using retrograde tracing combined with immunocytochemistry. Brain Res, 532, 329-332.

Yeomans, D.C. & Proudfit, H.K. (1992) Antinociception induced by microinjection of substance P into the A7 catecholamine cell group in the rat. Neuroscience, 49, 681-691.

Zhang, H.M., Chen, S.R., Cai, Y.Q., Richardson, T.E., Driver, L.C., Lopez-Berestein, G. & Pan, H.L. (2009) Signaling mechanisms mediating muscarinic enhancement of GABAergic synaptic transmission in the spinal cord. Neuroscience, 158, 1577-1588.

Zhang, Z., Reboreda, A., Alonso, A., Barker, P.A. & Seguela, P. (2010) TRPC channels underlie cholinergic plateau potentials and persistent activity in entorhinal cortex. Hippocampus.

Zhao, Y.Q., Zhang, N., Zhou, W., Tian, W. & Han, F.Y. (2005) [Change of gene expression pattern and regulation of SFK on the change in early stage after hemitransection of the spinal cord in rat]. Zhonghua Yi Xue Za Zhi, 85, 1982-1986.





QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔