RGD Reference Report - The kallikrein-kinin system: current and future pharmacological targets. - Rat Genome Database

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The kallikrein-kinin system: current and future pharmacological targets.

Authors: Moreau, ME  Garbacki, N  Molinaro, G  Brown, NJ  Marceau, F  Adam, A 
Citation: Moreau ME, etal., J Pharmacol Sci. 2005 Sep;99(1):6-38.
RGD ID: 7401223
Pubmed: PMID:16177542   (View Abstract at PubMed)

The kallikrein-kinin system is an endogenous metabolic cascade, triggering of which results in the release of vasoactive kinins (bradykinin-related peptides). This complex system includes the precursors of kinins known as kininogens and mainly tissue and plasma kallikreins. The pharmacologically active kinins, which are often considered as either proinflammatory or cardioprotective, are implicated in many physiological and pathological processes. The interest of the various components of this multi-protein system is explained in part by the multiplicity of its pharmacological activities, mediated not only by kinins and their receptors, but also by their precursors and their activators and the metallopeptidases and the antiproteases that limit their activities. The regulation of this system by serpins and the wide distribution of the different constituents add to the complexity of this system, as well as its multiple relationships with other important metabolic pathways such as the renin-angiotensin, coagulation, or complement pathways. The purpose of this review is to summarize the main properties of this kallikrein-kinin system and to address the multiple pharmacological interventions that modulate the functions of this system, restraining its proinflammatory effects or potentiating its cardiovascular properties.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BDKRB1HumanG protein mediated signaling pathway via Galphai family  TAS  RGD 
BDKRB2HumanG protein mediated signaling pathway via Galphai family  TAS  RGD 
Bdkrb1RatG protein mediated signaling pathway via Galphai family  ISOBDKRB1 (Homo sapiens) RGD 
Bdkrb1MouseG protein mediated signaling pathway via Galphai family  ISOBDKRB1 (Homo sapiens) RGD 
Bdkrb2RatG protein mediated signaling pathway via Galphai family  ISOBDKRB2 (Homo sapiens) RGD 
Bdkrb2MouseG protein mediated signaling pathway via Galphai family  ISOBDKRB2 (Homo sapiens) RGD 
BDKRB1HumanG protein mediated signaling pathway via Galphaq family  TAS  RGD 
BDKRB2HumanG protein mediated signaling pathway via Galphaq family  TAS  RGD 
Bdkrb1MouseG protein mediated signaling pathway via Galphaq family  ISOBDKRB1 (Homo sapiens) RGD 
Bdkrb1RatG protein mediated signaling pathway via Galphaq family  ISOBDKRB1 (Homo sapiens) RGD 
Bdkrb2MouseG protein mediated signaling pathway via Galphaq family  ISOBDKRB2 (Homo sapiens) RGD 
Bdkrb2RatG protein mediated signaling pathway via Galphaq family  ISOBDKRB2 (Homo sapiens) RGD 
A2MHumankallikrein-kinin cascade pathway   TAS  RGD 
A2mRatkallikrein-kinin cascade pathway   ISOA2M (Homo sapiens) RGD 
A2mMousekallikrein-kinin cascade pathway   ISOA2M (Homo sapiens) RGD 
ACEHumankallikrein-kinin cascade pathway   TAS  RGD 
AceRatkallikrein-kinin cascade pathway   ISOACE (Homo sapiens) RGD 
AceMousekallikrein-kinin cascade pathway   ISOACE (Homo sapiens) RGD 
BDKRB1Humankallikrein-kinin cascade pathway   TAS  RGD 
BDKRB2Humankallikrein-kinin cascade pathway   TAS  RGD 
Bdkrb1Mousekallikrein-kinin cascade pathway   ISOBDKRB1 (Homo sapiens) RGD 
Bdkrb1Ratkallikrein-kinin cascade pathway   ISOBDKRB1 (Homo sapiens) RGD 
Bdkrb2Mousekallikrein-kinin cascade pathway   ISOBDKRB2 (Homo sapiens) RGD 
Bdkrb2Ratkallikrein-kinin cascade pathway   ISOBDKRB2 (Homo sapiens) RGD 
CPMHumankallikrein-kinin cascade pathway   TAS  RGD 
CPN1Humankallikrein-kinin cascade pathway   TAS  RGD 
CpmRatkallikrein-kinin cascade pathway   ISOCPM (Homo sapiens) RGD 
CpmMousekallikrein-kinin cascade pathway   ISOCPM (Homo sapiens) RGD 
Cpn1Ratkallikrein-kinin cascade pathway   ISOCPN1 (Homo sapiens) RGD 
Cpn1Mousekallikrein-kinin cascade pathway   ISOCPN1 (Homo sapiens) RGD 
F12Humankallikrein-kinin cascade pathway   TAS  RGD 
F12Mousekallikrein-kinin cascade pathway   ISOF12 (Homo sapiens) RGD 
F12Ratkallikrein-kinin cascade pathway   ISOF12 (Homo sapiens) RGD 
KLK1Humankallikrein-kinin cascade pathway   TAS  RGD 
KLKB1Humankallikrein-kinin cascade pathway   TAS  RGD 
KNG1Humankallikrein-kinin cascade pathway   TAS  RGD 
Klk1Ratkallikrein-kinin cascade pathway   ISOKLK1 (Homo sapiens) RGD 
Klk1Mousekallikrein-kinin cascade pathway   ISOKLK1 (Homo sapiens) RGD 
Klkb1Mousekallikrein-kinin cascade pathway   ISOKLKB1 (Homo sapiens) RGD 
Klkb1Ratkallikrein-kinin cascade pathway   ISOKLKB1 (Homo sapiens) RGD 
Kng1Mousekallikrein-kinin cascade pathway   ISOKNG1 (Homo sapiens) RGD 
Kng2Ratkallikrein-kinin cascade pathway   ISOKNG1 (Homo sapiens) RGD 
MMEHumankallikrein-kinin cascade pathway   TAS  RGD 
SERPINA4Humankallikrein-kinin cascade pathway   TAS  RGD 
SERPING1Humankallikrein-kinin cascade pathway   TAS  RGD 
Serpina4Ratkallikrein-kinin cascade pathway   ISOSERPINA4 (Homo sapiens) RGD 
Serping1Ratkallikrein-kinin cascade pathway   ISOSERPING1 (Homo sapiens) RGD 
Serping1Mousekallikrein-kinin cascade pathway   ISOSERPING1 (Homo sapiens) RGD 
XPNPEP1Humankallikrein-kinin cascade pathway   TAS  RGD 
XPNPEP2Humankallikrein-kinin cascade pathway   TAS  RGD 
Xpnpep1Ratkallikrein-kinin cascade pathway   ISOXPNPEP1 (Homo sapiens) RGD 
Xpnpep1Mousekallikrein-kinin cascade pathway   ISOXPNPEP1 (Homo sapiens) RGD 
Xpnpep2Ratkallikrein-kinin cascade pathway   ISOXPNPEP2 (Homo sapiens) RGD 
Xpnpep2Mousekallikrein-kinin cascade pathway   ISOXPNPEP2 (Homo sapiens) RGD 
BDKRB1Humankinin signaling pathway   TAS  RGD 
BDKRB2Humankinin signaling pathway   TAS  RGD 
Bdkrb1Mousekinin signaling pathway   ISOBDKRB1 (Homo sapiens) RGD 
Bdkrb1Ratkinin signaling pathway   ISOBDKRB1 (Homo sapiens) RGD 
Bdkrb2Mousekinin signaling pathway   ISOBDKRB2 (Homo sapiens) RGD 
Bdkrb2Ratkinin signaling pathway   ISOBDKRB2 (Homo sapiens) RGD 
KNG1Humankinin signaling pathway   TAS  RGD 
Kng1Mousekinin signaling pathway   ISOKNG1 (Homo sapiens) RGD 
Kng2Ratkinin signaling pathway   ISOKNG1 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
A2m  (alpha-2-macroglobulin)
Ace  (angiotensin I converting enzyme)
Bdkrb1  (bradykinin receptor B1)
Bdkrb2  (bradykinin receptor B2)
Cpm  (carboxypeptidase M)
Cpn1  (carboxypeptidase N subunit 1)
F12  (coagulation factor XII)
Klk1  (kallikrein 1)
Klkb1  (kallikrein B1)
Kng2  (kininogen 2)
Serpina4  (serpin family A member 4)
Serping1  (serpin family G member 1)
Xpnpep1  (X-prolyl aminopeptidase 1)
Xpnpep2  (X-prolyl aminopeptidase 2)

Genes (Mus musculus)
A2m  (alpha-2-macroglobulin)
Ace  (angiotensin I converting enzyme)
Bdkrb1  (bradykinin receptor, beta 1)
Bdkrb2  (bradykinin receptor, beta 2)
Cpm  (carboxypeptidase M)
Cpn1  (carboxypeptidase N, polypeptide 1)
F12  (coagulation factor XII (Hageman factor))
Klk1  (kallikrein 1)
Klkb1  (kallikrein B, plasma 1)
Kng1  (kininogen 1)
Serping1  (serine (or cysteine) peptidase inhibitor, clade G, member 1)
Xpnpep1  (X-prolyl aminopeptidase (aminopeptidase P) 1, soluble)
Xpnpep2  (X-prolyl aminopeptidase (aminopeptidase P) 2, membrane-bound)

Genes (Homo sapiens)
A2M  (alpha-2-macroglobulin)
ACE  (angiotensin I converting enzyme)
BDKRB1  (bradykinin receptor B1)
BDKRB2  (bradykinin receptor B2)
CPM  (carboxypeptidase M)
CPN1  (carboxypeptidase N subunit 1)
F12  (coagulation factor XII)
KLK1  (kallikrein 1)
KLKB1  (kallikrein B1)
KNG1  (kininogen 1)
MME  (membrane metalloendopeptidase)
SERPINA4  (serpin family A member 4)
SERPING1  (serpin family G member 1)
XPNPEP1  (X-prolyl aminopeptidase 1)
XPNPEP2  (X-prolyl aminopeptidase 2)


Additional Information