Kinins, Receptors, Kininases and Inhibitors Where Did They Lead Us?
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Ervin G. Erdös
Abstract
Based on studies presented here and other published experiments performed with surviving tissue preparations, with transfected cells and with cells that constitutively express the human angiotensin I converting enzyme ACE and B2 receptors, we concluded the following: ACE inhibitors and other endogenous peptides that react with the active site of ACE potentiate the effect of bradykinin and its ACE resistant peptide congeners on the B2 receptor. They also resensitize receptors which had been desensitized by the agonist. ACE and bradykinin receptors have to be sterically close, possibly forming a heterodimer, for the ACE inhibitors to induce an allosteric modification on the receptor. When ACE inhibitors augment bradykinin effects, they reduce the phosphorylation of the B2 receptor. The primary actions of bradykinin on the receptor are not affected by protein kinase C or phosphatase inhibitors, but the potentiation of bradykinin or the resensitization of the receptor by ACE inhibitors are abolished by the same inhibitors. The results with protein kinase C and phosphatase inhibitors indicate that another intermediate protein may be involved in the processes of signaling induced by ACE inhibitors, and that ACE inhibitors affect the signal transduction pathway triggered by bradykinin on the B2 receptor.
Copyright © 2001 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- To Our Authors, Readers and Subscribers
- Kinins 1925-2000
- The Expanded Human Kallikrein (KLK) Gene Family: Genomic Organisation, Tissue-Specific Expression and Potential Functions
- Novel Roles of Kallistatin, a Specific Tissue Kallikrein Inhibitor, in Vascular Remodeling
- Signal Transduction from Bradykinin, Angiotensin, Adrenergic and Muscarinic Receptors to Effector Enzymes, Including ADP-Ribosyl Cyclase
- Classification of Kinin Receptors
- Metabolism-Resistant Bradykinin Antagonists: Development and Applications
- Kinins, Receptors, Kininases and Inhibitors Where Did They Lead Us?
- Bradykinin Signalling to MAP Kinase: Cell-Specific Connections versus Principle Mitogenic Pathways
- Kinins and Epithelial Ion Transport in the Alimentary Tract
- Role of the Renal Kallikrein-Kinin System in the Development of Salt-Sensitive Hypertension
- Role of the Light Chain of High Molecular Weight Kininogen in Adhesion, Cell-Associated Proteolysis and Angiogenesis
- Activation of the Kinin-Forming Cascade on the Surface of Endothelial Cells
- Kallikrein and Kinin Receptor Expression in Inflammation and Cancer
- Altered Neutrophil Homeostasis in Kinin B1 Receptor-Deficient Mice
- Cystatins as Calpain Inhibitors: Engineered Chicken Cystatin- and Stefin B-Kininogen Domain 2 Hybrids Support a Cystatin-Like Mode of Interaction with the Catalytic Subunit of µ-Calpain
- Synthetic Peptides and Fluorogenic Substrates Related to the Reactive Site Sequence of Kunitz-Type Inhibitors Isolated from Bauhinia: Interaction with Human Plasma Kallikrein
- Identification and Characterization of an Aromatic Amino Acid Decarboxylase from the Filarial Nematode, Dirofilaria immitis
- Molecular Cloning and Pharmacological Characterization of the Canine B1 and B2 Bradykinin Receptors
- Ligand-Mediated Regulation of Kinin Receptors in the Rabbit
- Activation of Sphingosine Kinase by the Bradykinin B2 Receptor and Its Implication in Regulation of the ERK/MAP Kinase Pathway
Articles in the same Issue
- To Our Authors, Readers and Subscribers
- Kinins 1925-2000
- The Expanded Human Kallikrein (KLK) Gene Family: Genomic Organisation, Tissue-Specific Expression and Potential Functions
- Novel Roles of Kallistatin, a Specific Tissue Kallikrein Inhibitor, in Vascular Remodeling
- Signal Transduction from Bradykinin, Angiotensin, Adrenergic and Muscarinic Receptors to Effector Enzymes, Including ADP-Ribosyl Cyclase
- Classification of Kinin Receptors
- Metabolism-Resistant Bradykinin Antagonists: Development and Applications
- Kinins, Receptors, Kininases and Inhibitors Where Did They Lead Us?
- Bradykinin Signalling to MAP Kinase: Cell-Specific Connections versus Principle Mitogenic Pathways
- Kinins and Epithelial Ion Transport in the Alimentary Tract
- Role of the Renal Kallikrein-Kinin System in the Development of Salt-Sensitive Hypertension
- Role of the Light Chain of High Molecular Weight Kininogen in Adhesion, Cell-Associated Proteolysis and Angiogenesis
- Activation of the Kinin-Forming Cascade on the Surface of Endothelial Cells
- Kallikrein and Kinin Receptor Expression in Inflammation and Cancer
- Altered Neutrophil Homeostasis in Kinin B1 Receptor-Deficient Mice
- Cystatins as Calpain Inhibitors: Engineered Chicken Cystatin- and Stefin B-Kininogen Domain 2 Hybrids Support a Cystatin-Like Mode of Interaction with the Catalytic Subunit of µ-Calpain
- Synthetic Peptides and Fluorogenic Substrates Related to the Reactive Site Sequence of Kunitz-Type Inhibitors Isolated from Bauhinia: Interaction with Human Plasma Kallikrein
- Identification and Characterization of an Aromatic Amino Acid Decarboxylase from the Filarial Nematode, Dirofilaria immitis
- Molecular Cloning and Pharmacological Characterization of the Canine B1 and B2 Bradykinin Receptors
- Ligand-Mediated Regulation of Kinin Receptors in the Rabbit
- Activation of Sphingosine Kinase by the Bradykinin B2 Receptor and Its Implication in Regulation of the ERK/MAP Kinase Pathway
