Kinin

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A kinin is any of various structurally related polypeptides, such as bradykinin and kallidin. [1] They are members of the autacoid family. [2] Kinins are peptides that are cleaved from kininogens by the process of kallikreins. Kallikreins activate kinins when stimulated. [3]

Contents

It is a component of the kinin-kallikrein system.

Their precursors are kininogens. [4] Kininogens contain a 9-11 amino acid bradykinin sequence. [5]

In botany, the plant hormones known as cytokinins were first called kinins, but the name was changed to avoid confusion. [6]

Effects of Kinins

Kinin are short lived peptides that cause pain sensation, arteriolar dilation, increase vascular permeability and cause contractions in smooth muscle. Kinins transmit their effects through G protein- coupled receptors. [5]

Kinin act on axons to block nervous impulses, which leads to distal muscle relaxation. Kinin are also potent nerve stimulators. which is mostly responsible for the sense of pain (and sometimes itching). Kinin increase vascular permeability by acting on vascular endothelial cells to cause cell contraction. Concomitantly they induce local expression of adhesive molecules. Together they increase leukocytes adhesion and extravasation. Kinin are rapidly inactivated by the proteases locally generated during the above-mentioned processes. [7]

They act locally to induce vasodilation and contraction of smooth muscle. [8] Kinins function as mediators for inflammatory responses by triggering the immune system. They are also able to regulate cardiovascular and renal function through mediating the effects of ACE inhibitors. [9] Reduced kinin activity can result in high blood pressure, sodium retention and the narrowing of blood vessels. [3]

Aspirin inhibits the activation of kallenogen by interfering with the formation of kallikrein enzyme which is essential in the process of activation.

Where kinins are produced

Kinins are mostly produced at inflamed or injured tissue of the body and human body fluids. Kinin peptides (kallidin and bradykinin) are located in human blood and urine. [10]

Kinin Receptors

There are two types of kinin receptors, B1 and B2. Both are G-protein coupled receptors in which B2 are expressed in various tissues and B1 are induced from inflammation, tissue injuries and stress. [11] The quantity of B2 receptors in the human body, exceed B1 receptors. [10]

B1 and B2 receptors are essentially related as homologous genes. [12] Both have the same cellular signaling pathways but, the patterns of the signaling pathway are different in the intensity and duration. B2 signaling pathway last only for a short time whereas BR1 signaling pathway undergoes longer. [13]

History

Kinin was initially discovered by J.E. Abelous and E. Bardier in 1909 when performing experiments utilizing human body fluids. Human body fluids such as urine was injected into dogs and it was observed that the urine caused a reduction in blood pressure. [3]

Related Research Articles

<span class="mw-page-title-main">Renin–angiotensin system</span> Hormone system

The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance.

<span class="mw-page-title-main">Atrial natriuretic peptide</span> Cardiac hormone which increases renal sodium excretion

Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides are a family of hormone/paracrine factors that are structurally related. The main function of ANP is causing a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion. ANP is synthesized and secreted by cardiac muscle cells in the walls of the atria in the heart. These cells contain volume receptors which respond to increased stretching of the atrial wall due to increased atrial blood volume.

<span class="mw-page-title-main">Bradykinin</span> Chemical compound

Bradykinin (BK) (Greek brady-, slow; -kinin, kīn(eîn) to move) is a peptide that promotes inflammation. It causes arterioles to dilate (enlarge) via the release of prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor and makes veins constrict, via prostaglandin F2, thereby leading to leakage into capillary beds, due to the increased pressure in the capillaries. Bradykinin consists of nine amino acids, and is a physiologically and pharmacologically active peptide of the kinin group of proteins.

<span class="mw-page-title-main">Angiotensin-converting enzyme</span> Mammalian protein found in humans

Angiotensin-converting enzyme, or ACE, is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasoconstrictor angiotensin II. Therefore, ACE indirectly increases blood pressure by causing blood vessels to constrict. ACE inhibitors are widely used as pharmaceutical drugs for treatment of cardiovascular diseases.

Mesangial cells are specialised cells in the kidney that make up the mesangium of the glomerulus. Together with the mesangial matrix, they form the vascular pole of the renal corpuscle. The mesangial cell population accounts for approximately 30-40% of the total cells in the glomerulus. Mesangial cells can be categorized as either extraglomerular mesangial cells or intraglomerular mesangial cells, based on their relative location to the glomerulus. The extraglomerular mesangial cells are found between the afferent and efferent arterioles towards the vascular pole of the glomerulus. The extraglomerular mesangial cells are adjacent to the intraglomerular mesangial cells that are located inside the glomerulus and in between the capillaries. The primary function of mesangial cells is to remove trapped residues and aggregated protein from the basement membrane thus keeping the filter free of debris. The contractile properties of mesangial cells have been shown to be insignificant in changing the filtration pressure of the glomerulus.

<span class="mw-page-title-main">Hereditary angioedema</span> Medical condition

Hereditary angioedema (HAE) is a disorder that results in recurrent attacks of severe swelling. The swelling most commonly affects the arms, legs, face, intestinal tract, and airway. If the intestinal tract is affected, abdominal pain and vomiting may occur. Swelling of the airway can result in its obstruction and trouble breathing. Without preventive treatment, attacks typically occur every two weeks and last for a few days.

High-molecular-weight kininogen is a circulating plasma protein which participates in the initiation of blood coagulation, and in the generation of the vasodilator bradykinin via the kallikrein-kinin system. HMWK is inactive until it either adheres to binding proteins beneath an endothelium disrupted by injury, thereby initiating coagulation; or it binds to intact endothelial cells or platelets for functions other than coagulation.

The kinin–kallikrein system or simply kinin system is a poorly understood hormonal system with limited available research. It consists of blood proteins that play a role in inflammation, blood pressure control, coagulation and pain. Its important mediators bradykinin and kallidin are vasodilators and act on many cell types. Clinical symptoms include marked weakness, tachycardia, fever, leukocytosis and acceleration of ESR.

Wilson Teixeira Beraldo was a Brazilian physician and physiologist, a co-discoverer of bradykinin.

Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein has no known paralogue, while tissue kallikrein-related peptidases (KLKs) encode a family of fifteen closely related serine proteases. These genes are localised to chromosome 19q13, forming the largest contiguous cluster of proteases within the human genome. Kallikreins are responsible for the coordination of various physiological functions including blood pressure, semen liquefaction and skin desquamation.

<span class="mw-page-title-main">Plasma kallikrein</span>

Plasma kallikrein is an enzyme. This enzyme catalyses the following chemical reaction

Kininogens are precursor proteins for kinins, biologically active polypeptides involved in blood coagulation, vasodilation, smooth muscle contraction, inflammatory regulation, and the regulation of the cardiovascular and renal systems.

The bradykinin receptor family is a group of G-protein coupled receptors whose principal ligand is the protein bradykinin.

<span class="mw-page-title-main">Kallidin</span> Chemical compound

Kallidin is a bioactive kinin formed in response to injury from kininogen precursors through the action of kallikreins.

<span class="mw-page-title-main">Natriuretic peptide</span>

A natriuretic peptide is a hormone molecule that plays a crucial role in the regulation of the cardiovascular system. These hormones were first discovered in the 1980s and were found to have very strong diuretic, natriuretic, and vasodilatory effects. There are three main types of natriuretic peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Two minor hormones include Urodilatin (URO) which is processed in the kidney and encoded by the same gene as ANP, and Dendroaspis NP (DNP) that was discovered through isolation of the venom from the green mamba snake. Since they are activated during heart failure, they are important for the protection of the heart and its tissues.

Bradykinin receptor B<sub>2</sub> Protein-coding gene in the species Homo sapiens

Bradykinin receptor B2 is a G-protein coupled receptor for bradykinin, encoded by the BDKRB2 gene in humans.

<span class="mw-page-title-main">Bradykinin receptor B1</span> Protein-coding gene in the species Homo sapiens

Bradykinin receptor B1 (B1) is a G-protein coupled receptor encoded by the BDKRB1 gene in humans. Its principal ligand is bradykinin, a 9 amino acid peptide generated in pathophysiologic conditions such as inflammation, trauma, burns, shock, and allergy. The B1 receptor is one of two of G protein-coupled receptors that have been found which bind bradykinin and mediate responses to these pathophysiologic conditions.

<span class="mw-page-title-main">Kininogen 1</span> Protein-coding gene in the species Homo sapiens

Kininogen-1 (KNG1), also known as alpha-2-thiol proteinase inhibitor, Williams-Fitzgerald-Flaujeac factor or the HMWK-kallikrein factor is a protein that in humans is encoded by the KNG1 gene. Kininogen-1 is the precursor protein to high-molecular-weight kininogen (HMWK), low-molecular-weight kininogen (LMWK), and bradykinin.

<span class="mw-page-title-main">Contact activation system</span>

In the contact activation system or CAS, three proteins in the blood, factor XII (FXII), prekallikrein (PK) and high molecular weight kininogen (HK), bind to a surface and cause blood coagulation and inflammation. FXII and PK are proteases and HK is a non-enzymatic co-factor. The CAS can activate the kinin–kallikrein system and blood coagulation through its ability to activate multiple downstream proteins. The CAS is initiated when FXII binds to a surface and reciprocal activation of FXII and PK occurs, forming FXIIa and PKa. FXIIa can initiate the coagulation cascade by cleaving and activating factor XI (FXI), which leads to formation of a blood clot. Additionally, the CAS can activate the kinin–kallikrein system when PKa cleaves HK to form cHK, releasing a peptide known as bradykinin (BK). BK and its derivatives bind to bradykinin receptors B1 and B2 to mediate inflammation.

<span class="mw-page-title-main">Marion Webster</span> American biochemist

Marion Elizabeth Webster-Bukovsky was a Canadian-American biochemist who was the first to isolate the Vi antigen of typhoid and to determine its structure. She published extensively on the kinin–kallikrein system while at the National Heart, Lung, and Blood Institute. Webster was an advocate for women in science and served as president of the Association for Women in Science and Graduate Women in Science.

References

  1. ↑ Kinins. De Gruyter. 2011. ISBN   978-3-11-025235-4.
  2. ↑ Kinins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  3. 1 2 3 Sharma, Jagdish N., ed. (2014). Recent Developments in the Regulation of Kinins. doi:10.1007/978-3-319-06683-7. ISBN   978-3-319-06682-0. S2CID   38701984.
  4. ↑ Online Medical Dictionary
  5. 1 2 Bader, Michael (2011-01-16), Bader, Michael (ed.), "1 Kinins: History and outlook", Kinins, Berlin, Boston: DE GRUYTER, pp. 1–6, doi:10.1515/9783110252354.1, ISBN   978-3-11-025235-4 , retrieved 2021-04-30
  6. ↑ Galuszka P, Spíchal L, Kopečný D, Tarkowski P, Frébortová J, Šebela M, Frébort I (2008). "Metabolism of plant hormones cytokinins and their function in signaling, cell differentiation and plant development". Bioactive Natural Products (Part N). Studies in Natural Products Chemistry. Vol. 34. pp. 203–64. doi:10.1016/S1572-5995(08)80028-2. ISBN   978-0-444-53180-3.
  7. ↑ Textbook Immunology: a short course, 5th ed, Coico R, Sunshine G, Benjamini E.Wiley-Liss
  8. ↑ " Kinin " at Dorland's Medical Dictionary
  9. ↑ Rhaleb NE, Yang XP, Carretero OA (April 2011). "The kallikrein-kinin system as a regulator of cardiovascular and renal function". Comprehensive Physiology. 1 (2): 971–93. doi:10.1002/cphy.c100053. ISBN   9780470650714. PMC   4685708 . PMID   23737209.
  10. 1 2 Duncan, Ann-Maree; Kladis, Athena; Jennings, Garry L.; Dart, Anthony M.; Esler, Murray; Campbell, Duncan J. (2000-04-01). "Kinins in humans". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 278 (4): R897–R904. doi: 10.1152/ajpregu.2000.278.4.r897 . ISSN   0363-6119. PMID   10749777.
  11. ↑ Soley, Bruna da Silva; Morais, Rafael Leite Tavares de; Pesquero, João Bosco; Bader, Michael; Otuki, Michel Fleith; Cabrini, Daniela Almeida (2016-05-01). "Kinin receptors in skin wound healing". Journal of Dermatological Science. 82 (2): 95–105. doi:10.1016/j.jdermsci.2016.01.007. ISSN   0923-1811. PMID   26817699.
  12. ↑ Girolami, Jean-Pierre; Bouby, Nadine; Richer-Giudicelli, Christine; Alhenc-Gelas, Francois (March 2021). "Kinins and Kinin Receptors in Cardiovascular and Renal Diseases". Pharmaceuticals. 14 (3): 240. doi: 10.3390/ph14030240 . ISSN   1424-8247. PMC   8000381 . PMID   33800422.
  13. ↑ da Costa, Patrícia L. N.; Sirois, Pierre; Tannock, Ian F.; Chammas, Roger (2014-04-01). "The role of kinin receptors in cancer and therapeutic opportunities". Cancer Letters. 345 (1): 27–38. doi: 10.1016/j.canlet.2013.12.009 . ISSN   0304-3835. PMID   24333733.
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