Mechanisms responsible for neuromuscular relaxation in the gastrointestinal tract;Mecanismos responsables de la relajación neuromuscular en el tracto gastrointestinal

Revista Espanola de Enfermedades Digestivas

Volumn 108, Issue 11, 2016, Pages 721-731

  Gallego, Diana ^a,b   Mañé, Noemí ^a   Gil, Víctor ^a   Martínez Cutillas, Miriam ^a   Jiménez, Marcel ^a,b  

^a INSTITUT DE NEUROCIÈNCIES   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

Author keywords

ATP; Enteric nervous system; Inhibitory neurotransmission; Nitric oxide; P2Y1 receptors

Indexed keywords

ADENOSINE TRIPHOSPHATE; NITRIC OXIDE; PURINERGIC P2 RECEPTOR; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS;

DIGESTIVE SYSTEM ELECTROPHYSIOLOGY; ENZYME ACTIVITY; GASTROINTESTINAL TRACT; HUMAN; HYPERPOLARIZATION; MOTONEURON; MOTOR DYSFUNCTION; MUSCLE RELAXATION; NEUROMUSCULAR FUNCTION; NEUROMUSCULAR TISSUE; NEUROMUSCULAR TRANSMISSION; NONHUMAN; PERISTALSIS; REVIEW; SIGNAL TRANSDUCTION; SPHINCTER; ANIMAL; INTESTINE INNERVATION; PHYSIOLOGY; SMOOTH MUSCLE; SYNAPTIC TRANSMISSION;

ANIMALS; ENTERIC NERVOUS SYSTEM; GASTROINTESTINAL TRACT; HUMANS; MUSCLE RELAXATION; MUSCLE, SMOOTH; NEUROTRANSMITTER AGENTS; SYNAPTIC TRANSMISSION;

EID: 85009854697     PISSN: 11300108     EISSN: None     Source Type: Journal    
DOI: 10.17235/reed.2016.4058/2016     Document Type: Review

References (98)

1. Kunze WA, Furness JB. The enteric nervous system and regulation of intestinal motility. Annu Rev Physiol 1999;61:117-42. DOI: 10.1146/ annurev.physiol.61.1.117
2. Furness JB. Types of neurons in the enteric nervous system. J Auton Nerv Syst 2000;81:87-96. DOI: 10.1016/S0165-1838(00)00127-2
3. Costa M, Brookes SJ, Hennig GW. Anatomy and physiology of the enteric nervous system. Gut 2000;47(Suppl. 4):iv15-iv19. DOI: 10.1136/gut.47.suppl_4.iv15
4. Brookes SJ. Classes of enteric nerve cells in the guinea-pig small intestine. Anat Rec 2001;262:58-70. DOI: 10.1002/1097-0185(20010101) 262:1<58::AID-AR1011>3.0.CO;2-V
5. Bertrand PP, Bornstein JC. ATP as a putative sensory mediator: Activation of intrinsic sensory neurons of the myenteric plexus via P2X receptors. J Neurosci 2002;22:4767-75.
6. Furness JB, Jones C, Nurgali K, et al. Intrinsic primary afferent neurons and nerve circuits within the intestine. Prog Neurobiol 2004;72:143-64. DOI: 10.1016/j.pneurobio.2003.12.004
7. Bornstein JC, Costa M, Grider JR. Enteric motor and interneuronal circuits controlling motility. Neurogastroenterol Motil 2004;16(Suppl. 1):34-8. DOI: 10.1111/j.1743-3150.2004.00472.x
8. Hansen MB. The enteric nervous system I: Organisation and classification. Pharmacol Toxicol 2003;92:105-13. DOI: 10.1034/j.1600-0773.2003.t01-1-920301.x
9. Lecci A, Santicioli P, Maggi CA. Pharmacology of transmission to gastrointestinal muscle. Curr Opin Pharmacol 2002;2:630-41. DOI: 10.1016/S1471-4892(02)00225-4
10. Linden DR, Levitt MD, Farrugia G, et al. Endogenous production of H2S in the gastrointestinal tract: Still in search of a physiologic function. Antioxid Redox Signal 2010;12:1135-46. DOI: 10.1089/ars.2009.2885
11. Sanger GJ, Broad J, Kung V, et al. Translational neuropharmacology: The use of human isolated gastrointestinal tissues. Br J Pharmacol 2013;168:28-43. DOI: 10.1111/j.1476-5381.2012.02198.x
12. Jiménez M, Clave P, Accarino A, et al. Purinergic neuromuscular transmission in the gastrointestinal tract; functional basis for future clinical and pharmacological studies. Br J Pharmacol 2014;171:4360-75. DOI: 10.1111/bph.12802
13. Sanders KM, Koh SD, Ro S, et al. Regulation of gastrointestinal motility - Insights from smooth muscle biology. Nat Rev Gastroenterol Hepatol 2012;9:633-45. DOI: 10.1038/nrgastro.2012.168
14. Bult H, Boeckxstaens GE, Pelckmans PA, et al. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature 1990;345:346-7. DOI: 10.1038/345346a0
15. González AA, Farre R, Clave P. Different responsiveness of excitatory and inhibitory enteric motor neurons in the human esophagus to electrical field stimulation and to nicotine. Am J Physiol Gastrointest Liver Physiol 2004;287:G299-306. DOI: 10.1152/ajpgi.00534.2003
16. Andrews CN, Bharucha AE, Camilleri M, et al. Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults. Am J Physiol Gastrointest Liver Physiol 2007;292:G1359-65.
17. Keef KD, Du C, Ward SM, et al. Enteric inhibitory neural regulation of human colonic circular muscle: Role of nitric oxide. Gastroenterology 1993;105:1009-16.
18. Stark ME, Bauer AJ, Sarr MG, et al. Nitric oxide mediates inhibitory nerve input in human and canine jejunum. Gastroenterology 1993;104:398-409.
19. Boeckxstaens GE, Pelckmans PA, Herman AG, et al. Involvement of nitric oxide in the inhibitory innervation of the human isolated colon. Gastroenterology 1993;104:690-7.
20. Tam FS, Hillier K. The role of nitric oxide in mediating non-adrenergic non-cholinergic relaxation in longitudinal muscle of human taenia coli. Life Sci 1992;51:1277-84. DOI: 10.1016/0024-3205(92)90017-J
21. O’Kelly T, Brading A, Mortensen N. Nerve mediated relaxation of the human internal anal sphincter: The role of nitric oxide. Gut 1993;34:689-93. DOI: 10.1136/gut.34.5.689
22. Shah V, Lyford G, Gores G, et al. Nitric oxide in gastrointestinal health and disease. Gastroenterology 2004;126:903-13. DOI: 10.1053/j.gas-tro.2003.11.046
23. De Man JG, De Winter BY, Herman AG, et al. Study on the cyclic GMP-dependency of relaxations to endogenous and exogenous nitric oxide in the mouse gastrointestinal tract. Br J Pharmacol 2007;150:88-96. DOI: 10.1038/sj.bjp.0706964
24. Gallego D, Gil V, Aleu J, et al. Purinergic and nitrergic junction potential in the human colon. Am J Physiol Gastrointest Liver Physiol 2008;295:G522-33. DOI: 10.1152/ajpgi.00510.2007
25. Gallego D, Malagelada C, Accarino A, et al. Nitrergic and purinergic mechanisms evoke inhibitory neuromuscular transmission in the human small intestine. Neurogastroenterol Motil 2014;26:419-29. DOI: 10.1111/nmo.12293
26. Mane N, Gil V, Martínez-Cutillas M, et al. Differential functional role of purinergic and nitrergic inhibitory cotransmitters in human colonic relaxation. Acta Physiol (Oxf) 2014;212:293-305. DOI: 10.1111/ apha.12408
27. Burnstock G, Campbell G, Satchell D, et al. Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut. Br J Pharmacol 1970;40:668-88. DOI: 10.1111/j.1476-5381.1970.tb10646.x
28. Burnstock G. Historical review: ATP as a neurotransmitter. Trends Pharmacol Sci 2006;27:166-76. DOI: 10.1016/j.tips.2006.01.005
29. Zagorodnyuk VP, Vladimirova IA, Vovk EV, et al. Studies of the inhibitory non-adrenergic neuromuscular transmission in the smooth muscle of the normal human intestine and from a case of Hirschsprung’s disease. J Auton Nerv Syst 1989;26:51-60. DOI: 10.1016/0165-1838(89)90107-0
30. Xue L, Farrugia G, Sarr MG, et al. ATP is a mediator of the fast inhibitory junction potential in human jejunal circular smooth muscle. Am J Physiol 1999;276:G1373-9.
31. Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Pharmacol Rev 1998;50:413-92.
32. Burnstock G, Knight GE. Cellular distribution and functions of P2 receptor subtypes in different systems. Int Rev Cytol 2004;240:31-304.
33. Burnstock G. Purinergic signalling in the gastrointestinal tract and related organs in health and disease. Purinergic Signal 2014;10:3-50. DOI: 10.1007/s11302-013-9397-9
34. Camaioni E, Boyer JL, Mohanram A, et al. Deoxyadenosine bisphosphate derivatives as potent antagonists at P2Y1 receptors. J Med Chem 1998;41:183-90. DOI: 10.1021/jm970433l
35. Cattaneo M, Lecchi A, Ohno M, et al. Antiaggregatory activity in human platelets of potent antagonists of the P2Y1 receptor. Biochem Pharmacol 2004;68:1995-2002. DOI: 10.1016/j.bcp.2004.06.026
36. Gallego D, Hernández P, Clave P, et al. P2Y1 receptors mediate inhibitory purinergic neuromuscular transmission in the human colon. Am J Physiol Gastrointest Liver Physiol 2006;291:G584-94. DOI: 10.1152/ ajpgi.00474.2005
37. Auli M, Martínez E, Gallego D, et al. Effects of excitatory and inhibitory neurotransmission on motor patterns of human sigmoid colon in vitro. Br J Pharmacol 2008;155:1043-55. DOI: 10.1038/bjp.2008.332
38. Kim HS, Barak D, Harden TK, et al. Acyclic and cyclopropyl analogues of adenosine bisphosphate antagonists of the P2Y1 receptor: Structure-activity relationships and receptor docking. J Med Chem 2001;44:3092-108. DOI: 10.1021/jm010082h
39. Boyer JL, Adams M, Ravi RG, et al. 2-Chloro N(6)-methyl-(N)-meth-anocarba-2’-deoxyadenosine-3’,5’-bisphosphate is a selective high affinity P2Y(1) receptor antagonist. Br J Pharmacol 2002;135:2004-10. DOI: 10.1038/sj.bjp.0704673
40. Gallego D, Gil V, Aleu J, et al. Pharmacological characterization of purinergic inhibitory neuromuscular transmission in the human colon. Neurogastroenterol Motil 2011;23:792-e338. DOI: 10.1111/j.1365-2982.2011.01725.x
41. Gallego D, Gil V, Martínez-Cutillas M, et al. Purinergic neuromuscular transmission is absent in the colon of P2Y(1) knocked out mice. J Physiol 2012;590:1943-56. DOI: 10.1113/jphysiol.2011.224345
42. Hwang SJ, Blair PJ, Durnin L, et al. P2Y1 purinoreceptors are fundamental to inhibitory motor control of murine colonic excitability and transit. J Physiol 2012;590:1957-72. DOI: 10.1113/jphysi-ol.2011.224634
43. Gil V, Martínez-Cutillas M, Mane N, et al. P2Y(1) knockout mice lack purinergic neuromuscular transmission in the antrum and cecum. Neurogastroenterol Motil 2013;25:e170-82. DOI: 10.1111/nmo.12060
44. HuHZ, Gao N, Zhu MX, et al. Slow excitatory synaptic transmission mediated by P2Y1 receptors in the guinea-pig enteric nervous system. J Physiol 2003;550:493-504. DOI: 10.1113/jphysiol.2003.041731
45. Wood JD. The enteric purinergic P2Y1 receptor. Curr Opin Pharmacol 2006;6:564-70. DOI: 10.1016/j.coph.2006.06.006
46. Mutafova-Yambolieva VN, Hwang SJ, Hao X, et al. Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle. Proc Natl Acad Sci U S A 2007;104:16359-64. DOI: 10.1073/pnas.0705510104
47. Hwang SJ, Durnin L, Dwyer L, et al. Beta-nicotinamide adenine dinucleotide is an enteric inhibitory neurotransmitter in human and nonhuman primate colons. Gastroenterology 2011;140:608-17. DOI: 10.1053/j.gastro.2010.09.039
48. Durnin L, Hwang SJ, Ward SM, et al. Adenosine 5-diphosphate-ribose is a neural regulator in primate and murine large intestine along with beta-NAD(+). J Physiol 2012;590:1921-41. DOI: 10.1113/jphysi-ol.2011.222414
49. Durnin L, Hwang SJ, Kurahashi M, et al. Uridine adenosine tetraphos-phate is a novel neurogenic P2Y1 receptor activator in the gut. Proc Natl Acad Sci USA 2014;111:15821-6. DOI: 10.1073/pnas.1409078111
50. Goyal RK. Evidence for beta-nicotinamide adenine dinucleotide as a purinergic, inhibitory neurotransmitter in doubt. Gastroenterology 2011;141:e27-8. DOI: 10.1053/j.gastro.2011.07.047
51. Goyal RK, Sullivan MP, Chaudhury A. Progress in understanding of inhibitory purinergic neuromuscular transmission in the gut. Neurogastroenterol Motil 2013;25:203-7. DOI: 10.1111/nmo.12090
52. Wang GD, Wang XY, Liu S, et al. Beta-nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum. Am J Physiol Gastrointest Liver Physiol 2015;308:G955-63. DOI: 10.1152/ajpgi.00430.2014
53. Bitar KN, Makhlouf GM. Relaxation of isolated gastric smooth muscle cells by vasoactive intestinal peptide. Science 1982;216:531-3. DOI: 10.1126/science.6176025
54. Tonini M, De Giorgio R, De Ponti F, et al. Role of nitric oxide- and vasoactive intestinal polypeptide-containing neurones in human gastric fundus strip relaxations. Br J Pharmacol 2000;129:12-20. DOI: 10.1038/sj.bjp.0702977
55. Schworer H, Clemens A, Katsoulis S, et al. Pituitary adenylate cyclase-activating peptide is a potent modulator of human colonic motility. Scand J Gastroenterol 1993;28:625-32. DOI: 10.3109/ 003655293090 96101
56. Farrugia G, Miller SM, Rich A, et al. Distribution of heme oxygenase and effects of exogenous carbon monoxide in canine jejunum. Am J Physiol 1998;274:G350-8.
57. Gibbons SJ, Farrugia G. The role of carbon monoxide in the gastrointestinal tract. J Physiol 2004;556:325-36. DOI: 10.1113/jphysi-ol.2003.056556
58. Gallego D, Clave P, Donovan J, et al. The gaseous mediator, hydrogen sulphide, inhibits in vitro motor patterns in the human, rat and mouse colon and jejunum. Neurogastroenterol Motil 2008;20:1306-16. DOI: 10.1111/j.1365-2982.2008.01201.x
59. Martínez-Cutillas M, Gil V, Mane N, et al. Potential role of the gaseous mediator hydrogen sulphide (H2S) in inhibition of human colonic contractility. Pharmacol Res 2015;93:52-63. DOI: 10.1016/j. phrs.2015.01.002
60. Lecea B, Gallego D, Farre R, et al. Regional functional specialization and inhibitory nitrergic and nonnitrergic coneurotransmission in the human esophagus. Am J Physiol Gastrointest Liver Physiol 2011;300:G782-94. DOI: 10.1152/ajpgi.00514.2009
61. Broad J, Hughes F, Chin-Aleong J, et al. Regionally dependent neuromuscular functions of motilin and 5-HT(4) receptors in human isolated esophageal body and gastric fundus. Neurogastroenterol Motil 2014;26:1311-22. DOI: 10.1111/nmo.12394
62. Broad J, Goralczyk A, Mannur K, et al. Drugs acting at 5-HT4, D2, motilin, and ghrelin receptors differ markedly in how they affect neuromuscular functions in human isolated stomach. Neurogastroenterol Motil 2014;26:851-61. DOI: 10.1111/nmo.12338
63. Mane N, Gil V, Martínez-Cutillas M, et al. Dynamics of inhibitory co-transmission, membrane potential and pacemaker activity determine neuromyogenic function in the rat colon. Pflugers Arch 2014;466:2305-21. DOI: 10.1007/s00424-014-1500-8
64. Mane N, Viais R, Martínez-Cutillas M, et al. Inverse gradient of nitrergic and purinergic inhibitory cotransmission in the mouse colon. Acta Physiol (Oxf). 2016;216:120-31. DOI: 10.1111/apha.12599
65. Keef KD, Saxton SN, McDowall RA, et al. Functional role of vasoactive intestinal polypeptide in inhibitory motor innervation in the mouse internal anal sphincter. J Physiol 2013;591:1489-1506. DOI: 10.1113/ jphysiol.2012.247684
66. Ward SM, Sanders KM. Interstitial cells of Cajal: Primary targets of enteric motor innervation. Anat Rec 2001;262:125-35. DOI: 10.1002/1097-0185(20010101)262:1<125::AID-AR1017>3.0.CO;2-I
67. Sanders KM. A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology 1996;111:492-515. DOI: 10.1053/gast.1996.v111.pm8690216
68. Kurahashi M, Nakano Y, Hennig GW, et al. Platelet-derived growth factor receptor alpha-positive cells in the tunica muscularis of human colon. J Cell Mol Med 2012;16:1397-404. DOI: 10.1111/j.1582-4934.2011.01510.x
69. Kurahashi M, Zheng H, Dwyer L, et al. A functional role for the ‘fibroblast-like cells’ in gastrointestinal smooth muscles. J Physiol 2011;589:697-710. DOI: 10.1113/jphysiol.2010.201129
70. Kurahashi M, Mutafova-Yambolieva V, Koh SD, et al. Platelet-derived growth factor receptor-alpha-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles. Am J Physiol Cell Physiol 2014;307:C561-70. DOI: 10.1152/ ajpcell.00080.2014
71. De Lorijn F, De Jonge WJ, Wedel T, et al. Interstitial cells of Cajal are involved in the afferent limb of the rectoanal inhibitory reflex. Gut 2005;54:1107-13. DOI: 10.1136/gut.2004.051045
72. Terauchi A, Kobayashi D, Mashimo H. Distinct roles of nitric oxide synthases and interstitial cells of Cajal in rectoanal relaxation. Am J Physiol Gastrointest Liver Physiol 2005;289:G291-9. DOI: 10.1152/ ajpgi.00005.2005
73. Lies B, Gil V, Groneberg D, et al. Interstitial cells of Cajal mediate nitrergic inhibitory neurotransmission in the murine gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 2014;307:G98-106. DOI: 10.1152/ajpgi.00082.2014
74. Ward SM, Sanders KM. Interstitial cells of Cajal: Primary targets of enteric motor innervation. Anat Rec 2001;262:125-35. DOI: 10.1002/1097-0185(20010101)262:1<125::AID-AR1017>3.0.CO;2-I
75. Peri LE, Sanders KM, Mutafova-Yambolieva VN. Differential expression of genes related to purinergic signaling in smooth muscle cells, PDG-FRalpha-positive cells, and interstitial cells of Cajal in the murine colon. Neurogastroenterol Motil 2013;25:e609-20. DOI: 10.1111/nmo.12174
76. Burns AJ, Lomax AE, Torihashi S, et al. Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach. Proc Natl Acad Sci USA 1996;93:12008-13. DOI: 10.1073/pnas.93.21.12008
77. Ward SM, Morris G, Reese L, et al. Interstitial cells of Cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters. Gastroenterology 1998;115:314-29. DOI: 10.1016/ S0016-5085(98)70198-2
78. Suzuki H, Ward SM, Bayguinov YR, et al. Involvement of intramuscular interstitial cells in nitrergic inhibition in the mouse gastric antrum. J Physiol 2003;546:751-63. DOI: 10.1113/jphysiol.2002.033365
79. Mearin F, Papo M, Malagelada JR. Impaired gastric relaxation in patients with achalasia. Gut 1995;36:363-8. DOI: 10.1136/gut.36.3.363
80. Shteyer E, Edvardson S, Wynia-Smith SL, et al. Truncating mutation in the nitric oxide synthase 1 gene is associated with infantile achalasia. Gastroenterology 2015;148:533-6. DOI: 10.1053/j.gastro.2014.11.044
81. Bortolotti M, Mari C, Lopilato C, et al. Sildenafil inhibits gastrodu-odenal motility. Aliment Pharmacol Ther 2001;15:157-61. DOI: 10.1046/j.1365-2036.2001.00917.x
82. Eherer AJ, Schwetz I, Hammer HF, et al. Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders. Gut 2002;50:758-64. DOI: 10.1136/gut.50.6.758
83. Kuiken SD, Vergeer M, Heisterkamp SH, et al. Role of nitric oxide in gastric motor and sensory functions in healthy subjects. Gut 2002;51:212-8. DOI: 10.1136/gut.51.2.212
84. Kuiken SD, Tytgat GN, Boeckxstaens GE. Role of endogenous nitric oxide in regulating antropyloroduodenal motility in humans. Am J Gastroenterol 2002;97:1661-7. DOI: 10.1016/S0002-9270(02)04180-1
85. Watkins CC, Sawa A, Jaffrey S, et al. Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy. J Clin Invest 2000;106:803. DOI: 10.1172/JCI8273C1
86. Vanormelingen C, Vanuytsel T, Masaoka T, et al. The normoglycaemic biobreeding rat: A spontaneous model for impaired gastric accommodation. Gut 2016;65:73-81. DOI: 10.1136/gutjnl-2014-308154
87. Grover M, Farrugia G, Lurken MS, et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology 2011;140:1575-85. DOI: 10.1053/j.gastro.2011.01.046
88. Sarnelli G, Sifrim D, Janssens J, et al. Influence of sildenafil on gastric sensorimotor function in humans. Am J Physiol Gastrointest Liver Physiol 2004;287:G988-92. DOI: 10.1152/ajpgi.00419.2003
89. He CL, Burgart L, Wang L, et al. Decreased interstitial cell of Cajal volume in patients with slow-transit constipation. Gastroenterology 2000;118:14-21. DOI: 10.1016/S0016-5085(00)70409-4
90. He CL, Soffer EE, Ferris CD, et al. Loss of interstitial cells of Cajal and inhibitory innervation in insulin-dependent diabetes. Gastroenterology 2001;121:427-34. DOI: 10.1053/gast.2001.26264
91. Espin F, Rofes L, Ortega O, et al. Nitrergic neuro-muscular transmission is up-regulated in patients with diverticulosis. Neurogastroenterol Motil 2014;26:1458-68. DOI: 10.1111/nmo.12407
92. Tjong YW, Ip SP, Lao L, et al. Role of neuronal nitric oxide synthase in colonic distension-induced hyperalgesia in distal colon of neonatal maternal separated male rats. Neurogastroenterol Motil 2011;23:666-e278. DOI: 10.1111/j.1365-2982.2011.01697.x
93. García-González MA, Peña AS. Nitric oxide and inflammatory bowel disease. Rev Esp Enferm Dig 1998;90:870-6.
94. Perner A, Rask-Madsen J. Review article: The potential role of nitric oxide in chronic inflammatory bowel disorders. Aliment Pharmacol Ther 1999;13:135-44. DOI: 10.1046/j.1365-2036.1999.00453.x
95. Martínez-Cutillas M, Mañé N, Gallego D, et al. EP2 and EP4 receptors mediate PGE2 induced relaxation in murine colonic circular muscle: Pharmacological characterization. Pharmacol Res 2014;90:76-86. DOI: 10.1016/j.phrs.2014.10.001
96. Chaudhury A, He XD, Goyal RK. Role of myosin Va in purinergic vesicular neurotransmission in the gut. Am J Physiol Gastrointest Liver Physiol 2012;302:G598-607. DOI: 10.1152/ajpgi.00330.2011
97. Idzko M, Ferrari D, Eltzschig HK. Nucleotide signalling during inflammation. Nature 2014;509:310-7. DOI: 10.1038/nature13085
98. Jiménez M, De Diego M, Martínez-Cutillas M, et al. Purinergic and nitrergic inhibitory neuromuscular transmission in ganglionic, transitional and aganglionic segments from Hirschsprung’s disease patients. Neurogastroenterol Motil 2015;27(S2):71Abs.