聲門運動端靠喉頭內收肌與外展肌調控。這兩群肌肉分別由喉返神經內收支與外展支支配，內收支具有呼氣活性，使內收肌在呼氣時收縮而縮小聲門面積；外展支於吸氣時期放電，活動時使外展肌收縮而擴大聲門孔徑。本實驗室最近的研究發現，辣椒素刺激肺迷走C纖維後會興奮喉返神經內收支與抑制外展支的活性並誘發聲門關閉。辣椒素為transient receptor potential vanilloid type 1 ( TRPV1 receptor) 的外生性致效劑，而與其結構相似的內生性脂質代謝物anandamide是否會經由活化肺迷走C纖維而改變上呼吸道的暢通至今還沒有相關的研究。Anandamide為一內生性的cannabinoid，已被證實可經由活化TRPV1接受器而興奮肺迷走C纖維，因此本研究擬探討TRPV1的內生性致效劑anandamide是否會影響喉返神經活性來調控喉頭的暢通。本實驗以雄性Wistar品系大白鼠為實驗動物並以urethane (1.2 g/kg) 腹腔麻醉，接著進行氣管插管、股動、靜脈插管，及頸靜脈插管。頸靜脈插管通向右心房，使注射的anandamide能進入肺循環興奮肺迷走C纖維。接著以gallamine thriethiodide (5 mg/kg，靜脈注射) 麻痺肌肉，接上人工呼吸器提供動物純氧。分離膈神經、喉返神經內收支及外展支並測量其活性。本實驗分為三部分，首先觀察不同劑量的anandamide (0.25、0.5及1 mg/kg) 是否會影響喉返神經內收支與外展支的活性。再者，因anandamide同時也是大麻鹼 (CB) 接受器的致效劑，因此第二部分實驗利用TRPV1與CB1接受器的拮抗劑來釐清anandamide影響喉返神經活性的作用是經由活化哪一類受器而產生。最後，利用數位相機拍攝聲門運動，觀察頸靜脈注射anandamide是否會改變自發性呼吸大鼠的聲門運動。實驗結果發現，中 (0.5 mg/kg) 與高劑量 (1 mg/kg) 的anandamide皆會引起肺化學反射，其特徵為呼吸暫停、降壓及抑心反應。此外，anandamide還會興奮喉返神經內收支並抑制外展支的活性，且使內收支由呼氣活動提前在吸氣時開始放電，外展支則由原本提前於膈神經前放電變為延遲。這些反應皆可被TRPV1拮抗劑 (capsazepine) 阻斷，但不受CB1拮抗劑 (AM281) 影響。第三部份結果顯示anandamide還可使聲門在呼吸暫停以及恢復期間緊緊關閉。這些結果顯示，anandamide可能是經由活化TRPV1接受器，引起反射作用來影響喉返神經內收支與外展支的活性，並進一步引起聲門關閉，同時也暗示著內生性的anandamide可能在病理情況之下經由興奮肺迷走C纖維來調控上呼吸道的暢通。

Vocal fold movement is modulated by the coordination of the laryngeal abducent muscles (abductor) and adducent muscles (adductor) during respiratory cycle. Contraction of the abductor which is supplied by the abducent branch of the recurrent laryngeal nerve (Abd RLN) widens the glottal aperture during inspiration, while contraction of the adductor which is innervated by the adducent branch of the RLN (Add RLN) narrows the glottis during expiration. Previous studies in our lab have shown that capsaicin-induced activation of pulmonary vagal C-fiber (PCF) receptors reflexively excites the Add RLN activity but inhibits the Abd RLN discharge, suggesting that the glottis is closed. It is not clear whether anandamide (AEA), an endogenous agonist of transient receptor potential vaniloid-1 (TRPV1, also called capsaicin receptor), might also elicit a similar reflex effect on the RLN as was induced by capsaicin. Aim of the present study was therefore to investigate whether AEA administration could produce a modulation of the glottal patency through activation of PCF receptors. Male Wistar rats were treated with atropine (0.5 mg/kg, i.p.) and then anesthetized with urethane (1.2 g/kg, i.p.). Catheterization of the femoral artery and vein, and jugular vein was performed for measuring blood pressure (BP) and drug administration, respectively. The animal was paralyzed and ventilated. Fractional concentration of carbon dioxide (FETCO2) was maintained at normocapnia in hyperoxia. In the first protocol, activities of the phrenic nerve (PNA), Add RLN (Add RLNA), and Abd RLN (Add RLNA) were examined in response to varied doses of AEA (0.25, 0.5 and 1 mg/kg). The present results showed that AEA administration evoked cardiopulmonary chemoreflex, characterized by apnea, hypotension, and bradycardia. An enhancement of Add RLNA during apneic period and recovery from apnea, reflecting an increase in amplitude and earlier onset during inspiration was dicerned. Concomitantly, a delay onset and decrease of Abd RLN discharge was observed. In the second protocol, pretreatment of TRPV1 antagonist capsazepine (CZP, 4.5 mg/kg) and CB1 antagonist AM281 (0.3 mg/kg) was performed to elucidate which one of these two receptors might be involved in AEA-induced changes in laryngeal functions. The RLN responses to AEA administration were abolished by pretreatment with capsazepine but not with AM 281. Finally, vocal fold movement was monitored using a digital camera under microscope in spontaneously breathing rats with simultaneously recording of diaphragmatic EMG activity. The observed results revealed that a tightly glottal closure was occurred during anandamide-induced apnea. These results suggest that anandamide-induced glottal closure is probably mediated through activation of TRPV1 on the PCF to produce a reflex modulation of the RLN activity.

1. Adachi T, Umezaki T, Matsuse T, Shin T. Changes in laryngeal muscle activities during hypercapnia in the cat. Otolaryngol Head Neck Surg 118:537-544, 1998.
2. Agostoni E, Chinnock JE, Daly M de B, Murray JG. Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat. J Physiol 135:182-205, 1957.
3. Balis UJ, Morris KF, Koleski J, Lindsey BG. Simulations of a ventrolateral medullary neural network for respiratory rhythmogenesis inferred from spike train cross-correlation. Biol Cybern 70:311-327, 1994.
4. Barillot JC, Grelot L, Reddad S, Bianchi AL. Discharge patterns of laryngeal motoneurones in the cat: an intracellular study. Brain Res 509:99-106, 1990.
5. Barnes PJ. Neurogenic inflammation in the airways. Respir Physiol 125:145-154, 2001.
6. Bartlett DJ. Upper airway motor systems. In Handbook for Physiology, Sec 3, the Respiratory System , Vol. II (eds Cherniack NS, Widdicombe JG), p. 223-245. Bethesda, MD: The American Physiological Society. 1986.
7. Bartlett DJ. Respiratory functions of the larynx. Physiol Rev 69: 33-57, 1989.
8. Begg M, Pacher P, Bátkai S, Osei-Hyiaman D, Offertáler L, Mo FM, Liu J, Kunos G. Evidence for novel cannabinoid receptors. Pharmacol Ther 106:133-145, 2005.
9. Biro T, Maurer M, Modarres S, Lewin NE, Brodie C, Acs G, Acs P, Paus R, Blumberg PM. Characterization of functional vanilloid receptors expressed by mast cells. Blood 91:1332-1340, 1998.
10. Bonz A, Laser M, Kullmer S, Kniesch S, Babin-Ebell J, Popp V, Ertl G, Wagner JA. Cannabinoids acting on CB1 receptors decrease contractile performance in human atrial muscle. J Cardiovasc Pharmacol 41:657-664, 2003.
11. Brancatisano A, Dodd DS, Engel LA. Posterior cricoarytenoid activity and glottic size during hyperpnea in humans. J Appl Physiol 71:977-982, 1991.
12. Calignano A, Katona I, Desarnaud F, Giuffrida A, La Rana G, Mackie K, Freund TF, Piomelli D. Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature 408:96-101, 2000.
13. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Natur 389:816-824, 1997.
14. Caulfield MP, Birdsall NJ. International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev 50:279-290, 1998.
15. Coleridge HM, Coleridge JC, Ginzel KH, Baker DG, Banzett RB, Morrison MA. Stimulation of 'irritant' receptors and afferent C-fibres in the lungs by prostaglandins. Nature 264:451-453, 1976.
16. Coleridge HM, Coleridge JC. Impulse activity in afferent vagal C-fibres with endings in the intrapulmonary airways of dogs. Respir Physiol 29:125-142, 1977.
17. Coleridge HM and Coleridge JCG. Reflexes evoked from tracheobronchial tree and lungs. In Handbook of Physiology: The Respiratory System. Control of Breathing. Bethesda, MD: Am. Physiol. Soc. sect. 3, vol. II, pt. 1, chapt. 12, p. 395-429, 1986.
18. Coleridge HM, Coleridge JC, Green JF, Parsons GH. Pulmonary C-fiber stimulation by capsaicin evokes reflex cholinergic bronchial vasodilation in sheep. J Appl Physiol 72:770-778, 1992.
19. Deutsch DG, Goligorsky MS, Schmid PC, Krebsbach RJ, Schmid HH, Das SK, Dey SK, Arreaza G, Thorup C, Stefano G, Moore LC. Production and physiological actions of anandamide in the vasculature of the rat kidney. J Clin Invest 100:1538-1546, 1997.
20. Deutsch DG, Ueda N, Yamamoto S. The fatty acid amide hydrolase (FAAH). Prostaglandins Leukot Essent Fatty Acids 66:201-210, 2002.
21. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946-1949, 1992.
22. Diaz V, Kianicka I, Letourneau P, Praud JP. Inferior pharyngeal constrictor electromyographic activity during permeability pulmonary edema in lambs. J Appl Physiol 81:1598-1604, 1996.
23. Diaz V, Dorion D, Renolleau S, Letourneau P, Kianicka I, Praud JP. Effects of capsaicin pretreatment on expiratory laryngeal closure during pulmonary edema in lambs. J Appl Physiol 86:1570-1577, 1999.
24. Di Marzo V, Fontana A, Cadas H, Schinelli S, Cimino G, Schwartz JC, Piomelli D. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372:686-691, 1994.
25. Di Marzo V, De Petrocellis L, Sepe N, Buono A. Biosynthesis of anandamide and related acylethanolamides in mouse J774 macrophages and N18 neuroblastoma cells. Biochem J 316:977-984, 1996.
26. Dreshaj IA, Haxhiu MA, Miller MJ, Abu-Shaweesh J, Martin RJ. Differential effects of hypercapnia on expiratory phases of respiration in the piglet. Respir Physiol 126:43-51, 2001.
27. Dutschmann M, Paton JF. Trigeminal reflex regulation of the glottis depends on central glycinergic inhibition in the rat. Am J Physiol 282: R999-R1005, 2002.
28. Dutschmann M, Paton JF. Dynamic changes in glottal resistance during exposure to severe hypoxia in neonatal rats in situ. Pediatr Res 58:193-198, 2005.
29. Egertová M, Elphick MR. Localisation of cannabinoid receptors in the rat brain using antibodies to the intracellular C-terminal tail of CB. J Comp Neurol 422:159-171, 2000.
30. Eichenwald EC, Ungarelli RA, Stark AR. Hypercapnia increases expiratory braking in preterm infants. J Appl Physiol 75:2665-2670, 1993.
31. England SJ, Bartlett D Jr, Daubenspeck JA. Influence of human vocal cord movements on airflow and resistance during eupnea. J Appl Physiol 52:773-779, 1982.
32. Estrada U, Brase DA, Martin BR, Dewey WL. Cardiovascular effects of delta-9- and delta-9(11)-tetrahydrocannabinol and their interaction with epinephrine. Life Sci 41:79-87, 1987.
33. Ezure K, Tanaka I, Kondo M. Glycine is used as a transmitter by decrementing expiratory neurons of the ventrolateral medulla in the rat. J Neurosci 23:8941-8948, 2003.
34. Felder CC, Nielsen A, Briley EM, Palkovits M, Priller J, Axelrod J, Nguyen DN, Richardson JM, Riggin RM, Koppe GA, Paul SM, Becker GW. Isolation and measurement of the endogenous cannabinoid receptor agonist, anandamide, in brain and peripheral tissues of human and rat. FEBS Lett 393:231-235, 1996.
35. Furusawa K, Yasuda K, Okuda D, Tanaka M, Yamaoka M. Central distribution and peripheral functional properties of afferent and efferent components of the superior laryngeal nerve: morphological and electrophysiological studies in the rat. J Comp Neurol 375:147-156, 1996.
36. Gardiner SM, March JE, Kemp PA, Bennett T. Complex regional haemodynamic effects of anandamide in conscious rats. Br J Pharmacol 135:1889-1896, 2002.
37. Gérard CM, Mollereau C, Vassart G, Parmentier M. Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J 279:129-134, 1991.
38. Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, Navarro M, Piomelli D. Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 2:358-363, 1999.
39. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC. Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87:1932-1936, 1990.
40. Ho CY, Gu Q, Lin YS, Lee LY. Sensitivity of vagal afferent endings to chemical irritants in the rat lung. Respir Physiol 127:113-124, 2001.
41. Holmes HR, Remmers JE. Stimulation of vagal C-fibers alters timing and distribution of respiratory motor output in cats. J Appl Physiol 67:2249-2256, 1989.
42. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161-202, 2002.
43. Inoue K, Koizumi S, Fuziwara S, Denda S, Inoue K, Denda M. Functional vanilloid receptors in cultured normal human epidermal keratinocytes. Biochem Biophys Res Commun 291:124-129, 2002.
44. Ishac EJ, Jiang L, Lake KD, Varga K, Abood ME, Kunos G. Inhibition of exocytotic noradrenaline release by presynaptic cannabinoid CB1 receptors on peripheral sympathetic nerves. Br J Pharmacol 118:2023-2028, 1996.
45. Johnstone RE, Lief PL, Kulp RA, Smith TC. Combination of delta-9-tetrahydrocannabinol with oxymorphone or pentobarbital: Effects on ventilatory control and cardiovascular dynamics. Anesthesiology 42:674-684, 1975.
46. Jones JF, Wang Y, Jordan D. Activity of C fibre cardiac vagal efferents in anaesthetized cats and rats. J Physiol 507:869-880, 1998.
47. Jordt SE, Tominaga M, Julius D. Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc Natl Acad Sci 97: 8134-8139, 2000.
48. Kaufman MP, Coleridge HM, Coleridge JC, Baker DG. Bradykinin stimulates afferent vagal C-fibers in intrapulmonary airways of dogs. J Appl Physiol 48:511-517, 1980.
49. Kopczyńska B. The contribution of VR1 and CB1 receptors and the role of the afferent vagal pathway in modelling of cardio-respiratory effects of anandamide in rats. Life Sci 80:1738-1745, 2007.
50. Kozak KR, Marnett LJ. Oxidative metabolism of endocannabinoids. Prostaglandins Leukot Essent Fatty Acids 66:211-220, 2002.
51. Kuna ST, Insalaco G, Villeponteaux DR, Vanoye CR, Smickley JS. Effect of hypercapnia and hypoxia on arytenoideus muscle activity in normal adult humans. J Appl Physiol 75:1781-1789, 1993.
52. Kwolek G, Zakrzeska A, Schlicker E, Göthert M, Godlewski G, Malinowska B. Central and peripheral components of the pressor effect of anandamide in urethane-anaesthetized rats. Br J Pharmacol 145:567-575, 2005.
53. Lai CJ and Kou YR. Stimulation of vagal pulmonary C fibers by inhaled wood smoke in rats. J Appl Physiol 84:30-36, 1998.
54. Lake KD, Martin BR, Kunos G, Varga K. Cardiovascular effects of anandamide in anesthetized and conscious normotensive and hypertensive rats. Hypertension 29:1204-1210, 1997.
55. Lee KZ, Lu IJ, Ku LC, Lin JT, Hwang JC. Response of respiratory-related hypoglossal nerve activity to capsaicin-induced pulmonary C-fiber activation in rats. J Biomed Sci 10:706-717, 2003.
56. Lee LY. Inhibitory effect of gas phase cigarette smoke on breathing: role of hydroxyl radical. Respir Physiol 82:227-238, 1990.
57. Lee LY, Pisarri TE. Afferent properties and reflex functions of bronchopulmonary C-fibers. Respir Physiol 125:47-65, 2001.
58. Lee MG, Weinreich D, Undem BJ. Effect of olvanil and anandamide on vagal C-fiber subtypes in guinea pig lung. Br J Pharmacol 146:596-603, 2005.
59. Li J, Kaminski NE, Wang DH. Anandamide-induced depressor effect in spontaneously hypertensive rats: role of the vanilloid receptor. Hypertension 41:757-762, 2003.
60. Lin YS, Lee LY. Stimulation of pulmonary vagal C-fibres by anandamide in anaesthetized rats: role of vanilloid type 1 receptors. J Physiol 539:947-955, 2002.
61. Liu J, Wang L, Harvey-White J, Osei-Hyiaman D, Razdan RK, Zhou Z, Chen A, Huang B, Kim HY, and Kunos G. A biosynthetic pathway for anandamide. Proc Natl Acad Sci USA 103:13345-13350, 2006.
62. Lu IJ, Ku LC, Lin JT, Lee KZ, Hwang JC. Pulmonary C-fiber activation enhances respiratory-related activities of the recurrent laryngeal nerve in rats. Chin J Physiol 45:143-154, 2002.
63. Lu IJ, Lee KZ, Lin JT, Hwang JC. Capsaicin administration inhibits the abducent branch but excites the thyroarytenoid branch of the recurrent laryngeal nerves in the rat. J Appl Physiol 98:1646-1652, 2005.
64. Lu IJ, Lee KZ, Hwang JC. Capsaicin-induced activation of pulmonary vagal C fibers produces reflex laryngeal closure in the rat. J Appl Physiol 101:1104-1112, 2006.
65. Malinowska B, Kwolek G, Göthert M. Anandamide and methanandamide induce both vanilloid VR1- and cannabinoid CB1 receptor-mediated changes in heart rate and blood pressure in anaesthetized rats. Naunyn Schmiedebergs Arch Pharmacol 364:562-569, 2001.
66. Mathew RJ, Wilson WH, Humphreys DF, Lowe JV, Wiethe KE. Regional cerebral blood flow after marijuana smoking. J Cereb Blood Flow Metab 12:750-758, 1992.
67. Matsuda LA, Bonner TI, Lolait SJ. Localization of cannabinoid receptor mRNA in rat brain. J Comp Neurol 327:535-550, 1993.
68. Matsumoto S. Effects of ammonia and histamine on lung irritant receptors in the rabbit. Respir Physiol 77:301-308, 1989.
69. Malit LA, Johnstone RE, Bourke DI, Kulp RA, Klein V, Smith TC. Intravenous delta-9-tetrahydrocannabinol: Effects of ventilatory control and cardiovascular dynamics. Anesthesiology 42:666-673, 1975.
70. Mezey E, Toth ZE, Cortright DN, Arzubi MK, Krause JE, Elde R, Guo A, Blumberg PM, Szallasi A. Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc Natl Acad Sci 97:3655-3660, 2000.
71. Millns PJ, Chapman V, Kendall DA. Cannabinoid inhibition of the capsaicin-induced calcium response in rat dorsal root ganglion neurones. Br J Pharmacol 132:969-971, 2001.
72. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61-65, 1993.
73. Nosaka S, Yasunaga K, Tamai S. Vagal cardiac preganglionic neurons: distribution, cell types, and reflex discharges. Am J Physiol 243:R92-R98, 1982.
74. O’Neil RG and Brown RC. The vanilloid receptor family of calcium-permeable channels: molecular integrators of microenvironmental stimuli. News Physiol Sci 18: 226-231, 2003.
75. Ono K, Shiba K, Nakazawa K, Shimoyama I. Synaptic origin of the respiratory-modulated activity of laryngeal motoneurons. Neurosciencse 140:1079-1088, 2006.
76. Palecek F, Sant’Ambrogio G, Sant’Ambrogio FB, Mathew OP. Reflex responses to capsaicin: intravenous, aerosol, and intratracheal administration. J Appl Physiol 67: 1428-1437, 1989.
77. Paton JF. Rhythmic bursting of pre- and post-inspiratory neurones during central apnoea in mature mice. J Physiol 502:623-639, 1997.
78. Paton JF, Dutschmann M. Central control of upper airway resistance regulating respiratory airflow in mammals. J Anat 201:319-323, 2002.
79. Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 74:129-180, 1997.
80. Pertwee RG. The pharmacology of cannabinoid receptors and their ligands: an overview. Int J Obes 30:S13-S18, 2006.
81. Poliaček I, Stránsky A, Jakuš J, Baráni H, Tomori Z, Halašová E. Activity of the laryngeal abductor and adductor muscles during cough, expiration and aspiration reflexes in cats. Physiol Res 52:749-762, 2003.
82. Praud JP, Canet E, Bureau MA. Chemoreceptor and vagal influences on thyroarytenoid muscle activity in awake lambs during hypoxia. J Appl Physiol 72:962-969, 1992.
83. Remmers JE, Richter DW, Ballantyne D, Bainton CR, Klein JP. Reflex prolongation of stage I of expiration. Pflugers Arch 407:190-198, 1986.
84. Richardson JD, Kilo S, Hargreaves KM. Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors. Pain 75:111-119, 1998.
85. Richter DW. Generation and maintenance of the respiratory rhythm. J Exp Biol 100:93-107, 1982.
86. Sasamura T, Sasaki M, Tohda C, Kuraidhi Y. Existence of capsaicin-sensitive glutamatergic terminals in rat hypothalamus. Neuroreport 9:2045-2048, 1998.
87. Satoh I, Shiba K, Kobayashi N, Nakajima Y, Konno A. Upper airway motor outputs during sneezing and coughing in decerebrate cats. Neurosci Res 32:131-135, 1998.
88. Schmid K, Niederhoffer N, Szabo B. Analysis of the respiratory effects of cannabinoids in rats. Naunyn Schmiedebergs Arch Pharmacol 368:301-308, 2003.
89. Schmid PC, Paria BC, Krebsbach RJ, Schmid HHO, Dey SK. Changes in anandamide levels in mouse uterus are associated with uterine receptivity for embryo implantation. Proc Natl Acad Sci USA 94:4188-4192, 1997.
90. Shiba K, Satoh I, Kobayashi N, Hayashi F. Multifunctional laryngeal motoneurons: an intracellular study in the cat. J Neurosci 19:2717-2727, 1999.
91. Smart D, Gunthorpe MJ, Jerman JC, Nasir S, Gray J, Muir AI, Chambers JK, Randall AD, Davis JB. The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1). Br J Pharmacol 129:227-230, 2000.
92. Smith PJ, McQueen DS. Anandamide induces cardiovascular and respiratory reflexes via vasosensory nerves in the anaesthetized rat. Br J Pharmacol 134:655-663, 2001.
93. Stengel PW, Rippy MK, Cockerham SL, Devane WA, Silbaugh SA. Pulmonary actions of anandamide, an endogenous cannabinoid receptor agonist, in guinea pigs. Eur J Pharmacol 355:57-66, 1998.
94. Sugiura T, Kondo S, Sukagawa A, Tonegawa T, Nakane S, Yamashita A, Waku K. Enzymatic synthesis of anandamide, an endogenous cannabinoid receptor ligand, through N-acylphosphatidylethanolamine pathway in testis: involvement of Ca21-dependent transacylase and phosphodiesterase activities. Biochem Biophys Res Commun 218:113-117, 1996.
95. Tognetto M, Amadesi S, Harrison S, Creminon C, Trevisani M, Carreras M, Matera M, Geppetti P, Bianchi A. Anandamide excites central terminals of dorsal root ganglion neurons via vanilloid receptor-1 activation. J Neurosci 21:1104-1109, 2001.
96. Tominaga M, Caterina MJ, Malmberg AB, Tosen TA, Gilvert H, Skinner K, Raumann BE, Basbaum AI, Julius D. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531-543, 1998.
97. Tucker RC, Kagaya M, Page CP, Spina D. The endogenous cannabinoid agonist, anandamide stimulates sensory nerves in guinea-pig airways. Br J Pharmacol 132:1127-1135, 2001.
98. Undem BJ, Chuaychoo B, Lee MG, Weinreich D, Myers AC, Kollarik M. Subtypes of vagal afferent C-fibres in guinea-pig lungs. J Physiol 556:905-917, 2004.
99. Varga K, Lake KD, Huangfu D, Guyenet PG, Kunos G. Mechanism of the hypotensive action of anandamide in anesthetized rats. Hypertension 28:682-686, 1995.
100. Veronesi B, Oortgiesen M, Carter JD, Devlin R. Particulate matter initiates inflammatory cytokine release by activation of capsaicin and acid receptors in a human bronchial epithelial cell line. Toxicol Appl Pharmacol 154: 106-115, 1999.
101. Vivian JA, Kishioka S, Butelman ER, Broadbear J, Lee KO, Woods JH. Analgesic, respiratory and heart rate effects of cannabinoid and opioid agonists in rhesus monkeys: antagonist effects of SR 141716A. J Pharmacol Exp Ther 286:697-703, 1998.
102. Wang AL, Blackford TL, Lee LY. Vagal bronchopulmonary C fiber and acute ventilatory responses to inhaled irritants. Respir Physiol 104:231-239, 1996.
103. Wang Y, Jones JF, Jeggo RD, de Burgh Daly M, Jordan D, Ramage AG. Effect of pulmonary C-fibre afferent stimulation on cardiac vagal neurones in the nucleus ambiguus in anaesthetized cats. J Physiol 526:157-165, 2000.
104. Wilson CG, Zhang Z, Bonham AC. Non-NMDA receptors transmit cardiopulmonary C fibre input in nucleus tractus solitarii in rats. J Physiol 496:773-785, 1996.
105. Wilson CG, Bonham AC. Effect of cardiopulmonary C fibre activation on the firing activity of ventral respiratory group neurones in the rat. J Physiol 504:453-466, 1997.
106. Yoshida Y, Miyazaki T, Hirano M, Shin T, Kanaseki T. Arrangement of motoneurons innervating the intrinsic laryngeal muscles of cats as demonstrated by horseradish peroxidase. Acta Otolaryngol 94:329-334, 1982.
107. Zhou D, Huang Q, St John WM, Bartlett D Jr. Respiratory activities of intralaryngeal branches of the recurrent laryngeal nerve. J Appl Physiol 67:1171-1178, 1989.
108. Zygmunt PM, Petersson J, An dersson DA, Chuang H, Sorgard M, Di Marzo V, Julius D, Hogestatt ED. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452-457, 1999.
109. 蔡緻怡、吳季瑾、李昆澤、黃基礎。M2蕈鹼接受器參與辣椒素引起大鼠抑心與降壓作用。BioFormosa 40:25-35，2005。