ПАТОГЕНЕТИЧЕСКИЕ ОСНОВЫ ХОЛИНОЛИТИЧЕСКОЙ ТЕРАПИИ И ВОЗМОЖНЫЕ МЕХАНИЗМЫ ЕЕ ПОТЕНЦИРОВАНИЯ ПОД ВЛИЯНИЕМ β2-АДРЕНОМИМЕТИКОВ
Аннотация
В настоящее время терапия ингаляционными бронхолитическими препаратами длительного и ультрадлительного действия является основой поддерживающей терапии хронической обструктивной болезни легких. В статье описаны патогенетические основы холинолитической терапии и возможные механизмы ее потенцирования под влиянием β2-адреномиметиков. Разрабатываются несколько фиксированных комбинаций холинолитиков и β2-адреномиметиков ультрадлительного действия. В 2013 г. в Европе зарегистрирована 1-я фиксированная комбинация, содержащая гликопирроний и индакатерол. Имеются все основания предполагать, что комбинация 2 типов бронхолитиков является фармакологически успешной: во-первых, добавление β2-адреноагонистов снижает высвобождение ацетилхолина (ACh) за счет изменения холинергической нейрональной передачи пресинаптическими β2-адренорецепторами, приводя к усилению релаксации гладких мышц бронхов, вызванной холинолитиками; во-вторых, добавление холинолитика может редуцировать констрикторный эффект ACh, чье высвобождение модулируется β2-адреноагонистами, и амплифицировать бронходилатацию, вызванную β2-адреноагонистами посредством прямой стимуляции β2-адренорецепторов.
Об авторах
В. И. Трофимов
ГБОУ ВПО "Первый Санкт-Петербургский государственный медицинский университет имени академика И.П.Павлова" Минздрава России: 197022, Санкт-Петербург, ул. Льва Толстого, 6–8
Россия
д. м. н., зав. кафедрой госпитальной терапии ГБОУ ВПО "ПСПГМУ им. акад. И.П.Павлова" Минздрава Рос-
сии, главный внештатный пульмонолог Северо-Западного региона; тел.: (921) 913-13-28
Россия
д. м. н., зав. кафедрой госпитальной терапии ГБОУ ВПО "ПСПГМУ им. акад. И.П.Павлова" Минздрава Рос-
сии, главный внештатный пульмонолог Северо-Западного региона; тел.: (921) 913-13-28
Л. Н. Сорокина
ГБОУ ВПО "Первый Санкт-Петербургский государственный медицинский университет имени академика И.П.Павлова" Минздрава России: 197022, Санкт-Петербург, ул. Льва Толстого, 6–8
Россия
д. м. н., доцент кафедры госпитальной терапии ГБОУ ВПО "ПСПГМУ им. акад. И.П.Павлова" Минздрава России; тел.: (921) 403-90-35
Россия
д. м. н., доцент кафедры госпитальной терапии ГБОУ ВПО "ПСПГМУ им. акад. И.П.Павлова" Минздрава России; тел.: (921) 403-90-35
Список литературы
1. Gosens R., Zaagsma J., Meurs H., Halayko A. J. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir. Res. 2006; 7: article 73.
2. Kistemaker L. E., Oenema T. A., Meurs H., Gosens R. Regulation of airway inflammation and remodeling by muscarinic receptors: perspectives on anticholinergic therapy in asthma and COPD. Life Sci. 2012; 91 (21–22): 1126–1133.
3. Gosens R., Bos I.S., Zaagsma J., Meurs H. Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling. Am. J. Respir. Crit. Care Med. 2005; 171: 1096–1102.
4. Caulfield M.P., Birdsall N.J.M. International union of pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol. Rev. 1998; 50 (2): 279–290.
5. Wessler I.K., Kirkpatrick C.J. The non-neuronal cholinergic system: an emerging drug target in the airways. Pulm. Pharmacol. Ther. 2001; 14 (6): 423–434.
6. Mak J.C., Barnes P.J. Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung. Am. Rev. Respir. Dis. 1990; 141 (1): 1559–1568.
7. Ramnarine S.I., Haddad E.B., Khawaja A.M. et al. On muscarinic control of neurogenic mucus secretion in ferret trachea. J. Physiol. (Lond.). 1996; 494: 577–586.
8. Ishihara H., Shimura S., Satoh M. et al. Muscarinic receptor subtypes in feline tracheal submucosal gland secretion. Am. J. Physiol. 1992; 262: 223–228.
9. Roffel A.F., Elzinga C.R., Van Amsterdam R.G. et al. Muscarinic M2 receptors in bovine tracheal smooth muscle: discrepancies between binding and function. Eur. J. Pharmacol. 1988; 153: 73–82.
10. Patel H.J., Barnes P.J., Takahashi T. et al. Evidence for prejunctional muscarinic autoreceptors in human and guinea pig trachea. Am. J. Respir. Crit. Care Med. 1995; 152 (3): 872–878.
11. ten Berge R.E.J., Zaagsma J., Roffel A.F. Muscarinic inhibitory autoreceptors in different generations of human airways. Am. J. Respir. Crit. Care Med. 1996; 154 (1): 43–49.
12. van Nieuwstadt R.A., Henricks P.A., Hajer R. et al. Characterization of muscarinic receptors in equine tracheal smooth muscle in vitro. Vet. Quart. 1997; 19 (2): 54–57.
13. Fisher J.T., Vincent S.G., Gomeza J. et al. Loss of vagally mediated bradycardia and bronchoconstriction in mice lacking M2 or M3 muscarinic acetylcholine receptors. FASEB J. 2004; 18 (6): 711–713.
14. Minette P.A., Lammers J.W., Dixon C.M. et al. A muscarinic agonist inhibits reflex bronchoconstriction in normal but not in asthmatic subjects. J. Appl. Physiol. 1989; 67 (6): 2461–2465.
15. Felder C.C. Muscarinic acetylcholine receptors: signal transduction through multiple effectors. FASEB J. 1995; 9 (8): 619–625.
16. Higashida H., Yokoyama S., Hashii M. et al. Muscarinic receptor-mediated dual regulation of ADP-ribosyl cyclase in NG108-15 neuronal cell membranes. J. Biol. Chem. 1997; 272 (50): 31272–31277.
17. White T.A., Kannan M.S., Walseth T.F. Intracellular calcium signaling through the cADPR pathway is agonist specific in porcine airway smooth muscle. FASEB J. 2003; 17 (3): 482–484.
18. Tliba O., Cidlowski J., Amrani Y. CD38 expression is insensitive to steroid action in cells treated with TNF-a and IFN-g by a mechanism involving the upregulation of glucocorticoid receptor b isoform. Mol. Pharmacol. 2006; 69 (2): 588–596.
19. Deshpande D.A., Walseth T.F., Panettieri R.A., Kannan M.S. CD38/cyclic ADP-ribose-mediated Ca2+ signaling contributes to airway smooth muscle hyper-responsiveness. FASEB J. 2003; 17 (3): 452–454.
20. Deshpande D.A., Dogan S., Walseth T.F. et al. Modulation of calcium signaling by interleukin-13 in human airway smooth muscle: role of CD38/cyclic adenosine diphosphate ribose pathway. Am. J. Respir. Cell Mol. Biol. 2004; 31 (1): 36–42.
21. Tliba O., Panettieri R.A. Jr, Tliba S. et al. Tumor necrosis factor-alpha differentially regulates the expression of proinflammatory genes in human airway smooth muscle cells by activation of interferon-beta-dependent CD38 pathway. Mol. Pharmacol. 2004; 66 (2): 322–329.
22. Hirshman C.A., Lande B., Croxton T.L. Role of M2 muscarinic receptors in airway smooth muscle contraction. Life Sci. 1999; 64: 443–448.
23. Yoshii A., Iizuka K., Dobashi K. et al. Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca2+sensitization. Am. J. Respir. Cell Mol. Biol. 1999; 20 (6): 1190–1200.
24. Janssen L.J., Wattie J., Lu-Chao H., Tazzeo T. Muscarinic excitationcontraction coupling mechanisms in tracheal and bronchial smooth muscles. J. Appl. Physiol. 2001; 91 (3): 1142–1151.
25. Schaafsma D., Gosens R., Bos I.S. et al. Allergic sensitization enhances the contribution of Rho-kinase to airway smooth muscle contraction. Br. J. Pharmacol. 2004; 143 (4): 477–484.
26. Chiba Y., Ueno A., Shinozaki K. et al. Involvement of RhoAmediated Ca2+ sensitization in antigen-induced bronchial smooth muscle hyperresponsiveness in mice. Respir. Res. 2005; 6: 4.
27. Chiba Y., Sakai H., Misawa M. Augmented acetylcholineinduced translocation of RhoA in bronchial smooth muscle from antigen-induced airway hyperresponsive rats. Br. J. Pharmacol. 2001; 133 (6): 886–890.
28. Chiba Y., Murata M., Ushikubo H. et al. Effect of cigarette smoke exposure in vivo on bronchial smooth muscle contractility in vitro in rats. Am. J. Respir. Cell Mol. Biol. 2005; 33 (6): 574–581.
29. ten Berge R.E., Santing R.E., Hamstra J.J. et al. Dysfunction of muscarinic M2 receptors after the early allergic reaction: possible contribution to bronchial hyperresponsiveness in allergic guinea-pigs. Br. J. Pharmacol. 1995; 114 (4): 881–887.
30. Coulson F.R., Fryer A.D. Muscarinic acetylcholine receptors and airway diseases. Pharmacol. Ther. 2003; 98 (1): 59–69.
31. Yang Z.J., Biggs D.F. Muscarinic receptors and parasympathetic neurotransmission in guinea-pig trachea. Eur. J. Pharmacol. 1991; 193 (3): 301–308.
32. On L.S., Boonyongsunchai P., Webb S. et al. Function of pulmonary neuronal M(2) muscarinic receptors in stable chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2001; 163 (6): 1320–1325.
33. Belmonte K.E. Cholinergic pathways in the lungs and anticholinergic therapy for chronic obstructive pulmonary disease. roc. Am. Thorac. Soc. 2005; 2 (4): 297–304; discuss.: 311–312.
34. Tashkin D.P., Fabbri L.M. Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents. Respir. Res. 2010; 11 (1): 149.
35. Undem B.J., Kollarik M. The role of vagal afferent nerves in chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc. 2005: 2 (4): 355-360; discuss. 371–372.
36. Spina D., Shah S., Harrison S. Modulation of sensory nerve function in the airways. Trends Pharmacol. Sci. 1998; 19 (11): 460–466.
37. Selivanova P.A., Kulikov E.S., Kozina O.V. et al. Differential expression of the b2-adrenoreceptor and M3-cholinoreceptor genes in bronchial mucosa of patients with asthma and chronic obstructive pulmonary disease. Ann. Allergy Asthma Immunol. 2012; 108 (1): 39–43.
38. Selivanova P.A., Kulikov E.S., Kozina O.V. et al. Morphological and molecular characteristics of "difficult" asthma. J. Asthma. 2010; 47 (3): 269–275.
39. Rogers D.F. Muscarinic control of airway mucus secretion. In: Zaagsma J., Meurs H., Roffel A.F., eds. Muscarinic Receptors in Airways Diseases. Basel; 2001: 175–201.
40. Rogers D.F. Airway mucus hypersecretion in asthma: an undervalued pathology? Curr. Opin. Pharmacol. 2004; 4 (3): 241–250.
41. Amishima M., Munakata M., Nasuhara Y. et al. Expression of epidermal growth factor and epidermal growth factor receptor immunoreactivity in the asthmatic human airway. Am. J. Respir. Crit. Care Med. 1998; 157 (6): 1907–1912.
42. Wessler I., Reinheimer T., Kilbinger H. et al. Increased acetylcholine levels in skin biopsies of patients with atopic dermatitis. Life Sci. 2003; 72 (18–19): 2169–2172.
43. Strom T.B., Deisseroth A., Morganroth J. et al. Alteration of the cytotoxic action of sensitized lymphocytes by cholinergic agents and activators of adenylate cyclase. Proc. Natl Acad. Sci. USA. 1972; 69 (10): 2995–2999.
44. Profita M., Giorgi R.D., Sala A. et al. Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD patients. Allergy. 2005; 60 (11): 1361–1369.
45. Bai T.R., Cooper J., Koelmeyer T. et al. The effect of age and duration of disease on airway structure in fatal asthma. Am. J. Respir. Crit. Care Med. 2000; 162 (2): 663–669.
46. Gosens R., Zaagsma J., Grootte Bromhaar M. et al. Acetylcholine: a novel regulator of airway smooth muscle remodelling? Eur. J. Pharmacol. 2004; 500: 193–201.
47. Grainge C.L., Lau L.C., Ward J.A. et al. Effect of bronchoconstriction on airway remodeling in asthma. N. Engl. J. Med. 2011; 364 (21): 2006–2015.
48. Matthiesen S., Kempkens S., Bahulayan A. et al. Muscarinic receptors mediate stimulation of human lung fibroblast proliferation. Am. J. Respir. Cell Mol. Biol. 2006; 35 (6): 621–627.
49. Krymskaya V.P., Orsini M.J., Eszterhas A.J. et al. Mechanisms of proliferation synergy by receptor tyrosine kinase and G protein-coupled receptor activation in human airway smooth muscle. Am. J. Respir. Cell Mol. Biol. 2000; 23 (4): 546–554.
50. Petrie G.R., Palmer K.N.V. Comparison of aerosol ipratropium bromide and salbutamol in chronic bronchitis and asthma. Br. Med. J. 1975; 1 (5955): 430–432.
51. Anthonisen N.R., Connett J.E., Kiley J.P. et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. J.A.M.A. 1994; 272 (19): 1497–1505.
52. Anzueto A., Tashkin D., Menjoge S., Kesten S. One-year analysis of longitudinal changes in spirometry in patients with COPD receiving tiotropium. Pulm. Pharmacol. Ther. 2005; 18: 75–81.
53. Zhang W.H., Zhang Y., Cui Y.Y. et al. Can beta-2-adrenoceptor agonists, anticholinergic drugs, and theophylline contribute to the control of pulmonary inflammation and emphysema in COPD? Fundam. Clin. Pharmacol. 2012; 26 (1): 118–134.
54. Cazzola M., Molimard M. The scientific rationale for combining long-acting beta-2-agonists and muscarinic antagonists in COPD. Pulm. Pharmacol. Ther. 2010; 23 (4): 257–267.
55. Dorinsky P.M., Reisner C., Ferguson G.T. et al. The combination of ipratropium and albuterol optimizes pulmonary function reversibility test in patients with COPD. Chest 1999; 115 (4): 966–971.
56. Easton P.A., Jadue C., Dhingra S., Anthonisen N.R. A comparison of the bronchodilating effects of a beta-2-adrenergic agent (albuterol) and an anticholinergic agent (ipratropium bromide), given by aerosol alone or in sequence. N. Engl. J. Med. 1986; 315 (12): 735–739.
57. LeDoux E.J., Morris J.F., Temple W.P., Duncan C. Standard and double dose ipratropium bromide and combined ipratropium bromide and inhaled meta-proterenol in COPD. Chest 1989; 95 (5): 1013–1016.
58. COMBIVENT Inhalation Aerosol Study Group. In chronic obstructive pulmonary disease, a combination of iprat- ropium and albuterol is more effective than either agent alone. An 85-day multicenter trial. Chest 1994; 105 (5): 1411–1419.
59. Levin D.C., Little K.S., Laughlin K.R. et al. Addition of anticholinergic solution prolongs bronchodilator effect of beta-2 agonists in patients with chronic obstructive pulmonary disease. Am. J. Med. 1996; 100: 40S–48S.
60. COMBIVENT Inhalation Solution Study Group. Routine nebulized ipratropium and albuterol together are better than either alone in COPD. Chest. 1997: 112: 1514–1521.
61. Sarria B., Naline E., Zhang Y. et al. Muscarinic M2 receptors in acetylcholine-isoproterenol functional antagonism in human isolated bronchus. Am. J. Physiol. Lung Cell Mol. Physiol. 2002; 283 (5): 1125–1132.
62. Canning B.J., Fischer A. Neural regulation of airway smooth muscle tone. Respir. Physiol. 2001; 125: 113–127.
63. Postma D.S., Keyzer J.J., Koeter G.H. et al. Influence of the parasympathetic and sympathetic nervous system on nocturnal bronchial obstruction. Clin. Sci. 1985; 69: 251–258.
64. Gaultier C., Reinberg A., Girard E. Circadian rhythms in lung resistance and dynamic lung compliance of healthy children. Effects of two bronchodilators. Respir. Physiol. 1977; 31 (2): 169–182.
65. Furlan R., Guzzetti S., Crivellaro W. et al. Continuous 24-hour assessment of the neural regulation of systemic arterial pressure and RR variabilities in ambulant subjects. Circulation 1990; 81 (2): 537–547.
66. Daniel E.E., Kannan M., Davis C., Posey-Daniel V. Ultrastructural studies on the neuromuscular control of human tracheal and bronchial muscle. Respir. Physiol. 1986; 63: 109–128.
67. Rhoden K.J., Meldrum L.A., Barnes P.J. Inhibition of cholinergic neurotransmission in human airways by β2-adrenoceptors. J. Appl. Physiol. 1988; 65: 700–705.
68. Aizawa H., Inoue H., Ikeda T. et al. Effects of procaterol, a b2-adrenoceptor stimulant, on neuroeffector transmission in human bronchial tissue. Respiration. 1991; 58: 163–166.
69. Zhang X.Y., Olszewski M.A., Robinson N.E. b2-Adrenoceptor activation augments acetylcholine release from tracheal parasympathetic nerves. Am. J. Physiol. 1995; 268: 950–956.
70. Kume H., Graziano M.P., Kotlikoff M.I. Stimulatory and inhibitory regulation of calcium-activated potassium channels by guanine nucleotide-binding proteins. Proc. Natl Acad. Sci. 1992; 89 (22): 11051–11055.
71. Patel H.J., Giembycz M.A., Keeling J.E. et al. Inhibition of cholinergic neurotransmission in guinea pig trachea by NS1619, a putative activator of large-conductance, calcium-activated potassium channels. J. Pharmacol. Exp. Ther. 1998; 286: 952–958.
72. Wedzicha Y.A., Decramer M., Ficker J.H. et al. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK):a randomised, doubleblind, parallel-group study. Lancet Respir. Med. 2013; 1 (3): 199–209.
73. Bateman E.D., Ferguson G.T., Barnes N. et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur. Respir. J. 2013; 42 (6): 1484–1494.
74. Vogelmeier C.F., Bateman E.D., Pallante J. et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study. Lancet Respir. Med. 2013; 1 (1): 51–60.
75. Dahl R., Jadayel D., Alagappan V.K. et al. Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponentsindacaterol and glycopyrronium: the BEACON study. Int. J. COPD. 2013; 8: 501–508.
Для цитирования:
Трофимов В.И., Сорокина Л.Н. ПАТОГЕНЕТИЧЕСКИЕ ОСНОВЫ ХОЛИНОЛИТИЧЕСКОЙ ТЕРАПИИ И ВОЗМОЖНЫЕ МЕХАНИЗМЫ ЕЕ ПОТЕНЦИРОВАНИЯ ПОД ВЛИЯНИЕМ β2-АДРЕНОМИМЕТИКОВ. Пульмонология. 2014;(2):91-99. https://doi.org/10.18093/0869-0189-2014-0-2-91-99
For citation:
Trofimov V.I., Sorokina L.N. MECHANISMS OF ANTICHOLINERGIC EFFECTS AND PROBABLE MECHANISMS OF THEIR POTENTIATION USING BETA-2-AGONISTS. PULMONOLOGIYA. 2014;(2):91-99. (In Russ.) https://doi.org/10.18093/0869-0189-2014-0-2-91-99
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