Kinins

Kinins......Page 4
Preface......Page 6
Contributors......Page 8
Contents......Page 12
1 Kinins: History and outlook......Page 18
References......Page 20
2.2 Kinins and kininogens......Page 24
2.3 Kallikreins......Page 27
2.4 Kininases......Page 31
2.5 Kinin receptors......Page 35
2.6 Genetics of the kallikrein-kinin system......Page 36
References......Page 39
3.3 Kinin binding sites in the receptors......Page 50
3.4 Receptor maturation and cellular distribution......Page 51
3.5.1 Agonist-stimulated receptor signaling......Page 52
3.5.3 Roles of proteases in receptor signaling......Page 54
3.6.1 Receptor gene regulation......Page 55
3.6.3 Receptor trafficking......Page 57
References......Page 59
4.2 Animal models for the study of kinins......Page 68
4.3.1 B1 receptor knockout models......Page 69
4.3.2 B1R overexpression models......Page 72
4.3.3 Models of tissue-specific expression of B1 receptor......Page 73
4.4 B2 receptor transgenic models......Page 74
4.5 B1 and B2 receptor knockout model......Page 77
References......Page 80
5.2 Plasma kallikrein inhibitors......Page 86
5.4 B2R antagonists......Page 88
5.5 B2R agonists......Page 91
5.6 B1R antagonists......Page 92
5.8 ACE inhibitors......Page 93
5.10 Other considerations......Page 94
References......Page 95
6.2 Kallikrein-kinin system and kinins in neural tissue and brain......Page 102
6.2.2 Kallikrein levels......Page 103
6.3.1 Expression of kinin receptors and their functions in the brain......Page 104
6.3.2 Kinin receptors and their functions in astrocytes......Page 105
6.3.3 Kinin receptors and their functions in microglia......Page 106
6.4.1 Memory impairment in AD and BK receptors......Page 108
6.4.2 Epilepsy and kinin receptors......Page 110
6.4.4 Hypertension and kinin receptors in the brain......Page 111
6.4.5 Kinins and brain infl ammation......Page 112
References......Page 113
7.1.3 Kinin receptors......Page 120
7.2 Kidney development......Page 121
7.3.1 Renal blood flow......Page 122
7.3.2 Urinary excretion......Page 123
7.5 Glomerular injury......Page 124
7.6 Tubulointerstitial fibrosis......Page 125
References......Page 127
8.2 The local cardiac KKS under physiological conditions......Page 134
8.3.1 The local cardiac KKS......Page 135
8.3.3 The influence of the KKS on endothelial dysfunction and inflammation......Page 136
8.3.4 The influence of the KKS on the extracellular matrix......Page 137
8.3.5 The effects of the KKS on intracellular Ca2+ -handling......Page 138
8.3.6 The KKS and angiogenesis......Page 139
8.4.2 The role of the KKS on cardiac left ventricular remodeling......Page 140
8.5 The role of the KKS in post ischemic angiogenesis, neovascularization, and stem cell recruitment......Page 143
References......Page 144
9.2.1 Developmental expression of the KKS......Page 154
9.2.3 Insights from genetically modifi ed animals......Page 156
9.3 The rise and plunge of vasodilatory theory: a suspended verdict......Page 157
9.4 Involvement of the KKS in vessel growth......Page 158
9.5 Involvement of the KKS in atherosclerotic vessel wall remodeling and vascular repair......Page 160
References......Page 162
10.1 The skin: a defensive barrier......Page 172
10.2 Kallikreins, kinins, and kinin receptors in the skin......Page 173
10.3.1 Cell differentiation and skin desquamation......Page 174
10.3.2 Contribution of kallikreins to innate immunity and wound healing......Page 176
10.4 Kinin receptors and EGFR transactivation......Page 177
10.5 Kinin receptors and keratinocyte differentiation......Page 178
References......Page 181
11.2.1 Two pathways for kinin production......Page 188
11.3.1 Localization of KKS components in ocular structure......Page 190
11.4.1 Retinal vascular functions......Page 192
11.4.2 Neuroretinal functions......Page 194
11.4.3 Aqueous outflow facility......Page 195
11.4.6 Ciliary artery dilatation......Page 196
11.5.2 Diabetic macular edema......Page 197
Acknowledgments......Page 198
References......Page 199
12.2.1 Kininogens......Page 204
12.2.2 Kallikrein-related peptidases......Page 205
12.2.3 Bradykinin receptor......Page 206
12.2.4 Kininases......Page 209
12.2.5 Involvement of the KKS in the physiology of male reproductive organs......Page 210
12.3.2 Kallikrein-related peptidases......Page 212
12.3.5 Involvement of the KKS in the physiology of female reproductive organs......Page 213
References......Page 214
13.2 Plasmatic coagulation......Page 220
13.3 FXII and the intrinsic pathway of blood coagulation......Page 221
13.4 Deficiency in contact factors protects from thrombosis......Page 223
13.5 Role of contact factors for thromboembolic disease in humans......Page 224
13.6 Putting the contact into contact activation......Page 226
13.7 Polyphosphates: the endogenous activator of FXII in thrombosis......Page 227
References......Page 229
14.2.1 Classical kallikreins......Page 234
14.2.3 Kinins......Page 235
14.2.4 Kinin receptors......Page 236
14.3 The kinin system and tumor microenvironment......Page 237
14.4.1 Mitogenic kinins......Page 239
14.4.2 Kinin receptors......Page 240
14.4.3 Kinin receptor antagonists......Page 241
14.5 True tissue kallikrein and kinin receptors in human tumors......Page 242
14.5.1 Breast cancer......Page 243
14.5.2 Glioblastoma......Page 246
14.5.3 Astrocytomas......Page 247
14.5.5 Prostate cancer......Page 248
14.5.7 Esophageal and gastric cancer......Page 249
14.5.11 Chondrosarcoma......Page 250
14.6 Kallikrein-related peptidases (KLK2-KLK15/hK2-KLK15)......Page 251
References......Page 252
15.1 Introduction......Page 264
15.2 Kinins and infl ammatory pain......Page 265
15.3 Kinins and visceral pain......Page 267
15.4 Kinins and neuropathic pain......Page 268
15.5 Kinins and cancer/chemotherapy pain......Page 270
15.6 Kinins and itch......Page 271
References......Page 272
16.1 Introduction......Page 278
16.2 The KKS in inflammation......Page 279
16.3 B2R and the initiation of inflammation......Page 280
16.4 B1R and the progression of inflammation......Page 282
16.5 B1R and monocytes/macrophages......Page 284
16.6 KKS and the adaptive immune response......Page 285
References......Page 286
17.2.1 ACE and diabetic nephropathy......Page 290
17.2.2 Kinin receptors and diabetic nephropathy......Page 292
17.4 KKS and diabetic neuropathy......Page 294
17.6 Nitric oxide mediates the beneficial effect of KKS on diabetic complications......Page 295
17.7 Role of oxidative metabolism in preventing diabetic complications by KKS......Page 296
17.8 Therapeutic implications......Page 297
References......Page 298
18.1.1.1 Angioedema not responsive to antihistamine......Page 306
18.1.1.2 Angioedema due to C1-inhibitor deficiency......Page 307
18.1.1.4 Idiopathic non-histaminergic angioedema......Page 308
18.2.1 C1-inhibitor deficiency and the generation of bradykinin......Page 309
18.2.1.2 Pathophysiology of angioedema due to C1-inhibitor deficiency......Page 311
18.2.2 ACE inhibitors and the catabolism of bradykinin......Page 312
18.2.3 Bradykinin involvement in idiopathic angioedema......Page 313
18.3.1 C1-inhibitor replacement......Page 314
18.3.2 Kallikrein inhibition......Page 315
18.3.4 Inhibition of the fibrinolytic system......Page 316
References......Page 317
19.2 Kinin release by microorganisms......Page 324
19.3.1 Activation of FXII or PK......Page 325
19.3.2 Release from kininogens......Page 327
19.4 Kinin release at the surface of the microorganism......Page 328
19.5.1 Degradation of kinins by microorganisms......Page 329
19.6 Kinin receptor regulation......Page 330
19.7 Pathological consequences of kinin release by bacterial pathogens......Page 331
19.9 Concluding remarks......Page 332
References......Page 333
20.2.1 History and epidemiology of Chagas’ disease......Page 338
20.2.2 T. cruzi life cycle and the pathogenesis of Chagas’ disease......Page 339
20.2.3 T. cruzi expresses kinin -releasing cysteine proteases......Page 340
20.2.4 T. cruzi invades cardiovascular cells through the activation of kinin receptors......Page 341
20.2.5 Interstitial edema is orchestrated by a transcellular “cross-talk” between TLR2, CXCR2, and B2R......Page 342
20.2.6 Kinins steer TH1 polarization through the activation of dendritic cells......Page 345
20.2.7 Kinins orchestrate protective immune responses against systemic T. cruzi infection......Page 346
20.3.1 Leishmania life cycle and interplay with sand fly saliva......Page 347
20.3.3 Visceral leishmaniasis and the KKS......Page 348
References......Page 350
21.1 Introduction......Page 354
21.2.1 Kinin receptors......Page 356
21.2.2 Kallikreins and serine protease inhibitors......Page 360
21.2.3 Coagulation factor XII (FXII )......Page 362
21.3.1 Kinin receptors......Page 363
21.3.2 Kallikreins and serine protease inhibitors......Page 364
References......Page 365
Index......Page 372