Kinins

kinins description

1. KININS Bhagya Siripalli , Department of Pharmacology , SVIPS.

2. A kinin is any of various structurally related polypeptides such as bradykinin and kallidin. They are members of the autocoid family. They act locally to induce vasodilation and contraction of smooth muscle. They induce a variety of effects via the activation of specific B1 or B2 receptors . I t is a component of the  kinin-kallikrein system.Their precursors are  kininogens . I n  botany, the plant hormones known as  cytokinins  were first called kinins , but the name was changed to avoid confusion .

3. Physiological Functions of bradykinin/kallidin Pain B2 receptors in NS localised to sites involving nociception such as superf.layers spinal cord, thin un myelinated fibres, and cells in sensory ganglia where stimulation elicits pain. Renal Function R enal kallikrein involved in local regulation renal function. I ncr . electrogenic transport of Cl in collecting duct via stimulation of receptors on basolat. surface of tubule cell. BP R ole in regulation BP as kininase II same as ACE. K inins may blunt effect of pressor agents.

4. Inflammation K inins mimic manifestations of inflammation: I nhaled Ag or rhinoviral rhinitis. H ereditary angio edema (HAE) (defect in C1 esterase inhibitors) R ole in inflammation. response in gout, endotoxic shock, DIC

5. Kinin–kallikrein system 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. History The system was discovered in 1909 when researchers discovered that injection with urine (high in kinins ) led to hypotension (low blood pressure). The researchers  Emil Karl Frey ,  Heinrich Kraut  and  Eugen Werle  discovered high-molecular weight kininogen  in urine around 1930.

6. MEMBERS The system consists of a number of large proteins, some small polypeptides and a group of enzymes that activate and deactivate the compounds. Proteins High-molecular weight kininogen  (HMWK) and  low-molecular weight kininogen  (LMWK) are precursors of the polypeptides. They have no activity of themselves. HMWK is produced by the liver together with prekallikrein (see below). It acts mainly as a cofactor on coagulation and inflammation, and has no intrinsic catalytic activity. LMWK is produced locally by numerous tissues, and secreted together with tissue kallikrein . Polypeptides Bradykinin  (BK), which acts on the B2 receptor and slightly on B1, is produced when kallikrein releases it from HMWK. It is a nonapeptide with the amino acid sequence Arg –Pro–Pro– Gly – Phe –Ser–Pro– Phe –Arg. Kallidin  (KD) is released from LMWK by tissue kallikrein . It is a decapeptide . KD has the same amino acid sequence as Bradykinin with the addition of a Lysine at the N-terminus, thus is sometimes referred to as Lys- Bradykinin .

7. ENZYMES Kallikreins  (tissue and plasma kallikrein ) are serine proteases that liberate kinins  (BK and KD) from the kininogens , which are plasma proteins that are converted into vasoactive peptides.  Prekallikrein  is the precursor of plasma kallikrein . It can only activate kinins after being activated itself by factor XIIa  or other stimuli. Carboxypeptidases  are present in two forms: N circulates and M is membrane-bound. They remove arginine residues at the carboxy -terminus of BK and KD. Angiotensin converting enzyme  (ACE), also termed  kininase II , inactivates a number of peptide mediators, including  bradykinin . It is better known for activating angiotensin. Neutral endopeptidase  also deactivates kinins and other mediators.

8. PHARMACOLOGY Inhibition of ACE with  ACE inhibitors  leads to decreased conversion of angiotensin I to angiotensin II (a vasoconstrictor) but also to an increase in bradykinin due to decreased degradation. This explains why some patients taking ACE inhibitors develop a dry cough, and some react with  angioedema , a dangerous swelling of the head and neck region. There are hypotheses that many of the ACE-inhibitors' beneficial effects are due to their influence on the kinin-kallikrein system . This includes their effects in arterial hypertension, in ventricular remodeling (after myocardial infarction) and possibly diabetic nephropathy. Role in disease Defects of the kinin-kallikrein system in diseases are not generally recognized. It is known that kinins are inflammatory mediators that cause dilation of blood vessels and increased vascular permeability. Kinins are small peptides produced from kininogen by kallikrein and are broken down by kininases . They act on phospholipase and increase  arachidonic acid release and thus prostaglandin (PGE2) production.

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