Heparin antagonism

Heparin antagonism. Heparin effects wear off so rapidly that an antagonist is seldom required except after extracorporeal perfusion for heart surgery. Protamine, a protein obtained from fish sperm, reverses the anticoagulant action of heparin, when antagonism is needed. It is as strongly basic as heparin is acidic, which explains its immediate action. Protamine sulphate, 1 mg by slow i.v. injection, neutralises about 100 units of heparin derived from mucosa (mucous) or 80 units of heparin from lung ... 

In contrast to heparin, the coumarinic acid anticoagulants are inactive in vitw ]6k.e heparin they are active in vivo. The phenylindanedione-type compounds (7) (36) and warfarin (2) produce their in vivo inhibitory effect on the coagulation system by competitively antagonizing the normal activity of vitamin (8) (37—44). 

Capacitative Ca2+ entry is the predominant mode of regulated Ca2+ entry in nonexcitable cells but it also occurs in a number of excitable cell types. This pathway of Ca2+ entry is usually associated with the activation of phospholipase C, which mediates the formation of IP3 (see Ch. 20). Intracellular application of IP3 mimics the ability of hormones and neurotransmitters to activate calcium ion entry, and activation of calcium ion entry by hormones and neurotransmitters can be blocked by intracellular application of low-molecular-weight heparin, which potently antagonizes IP3 binding to its receptor. There is considerable evidence for the presence of an IP3 receptor in the plasma membrane of some cells types. 1(1,3,4,5)P4, a product of IP3 phosphorylation, has been shown in some cells to augment this action of IP3 in activating PM calcium ion entry, but in others IP3 alone is clearly sufficient. 

Other drugs affect intracellular calcium channels of the endoplasmic or sarcoplasmic reticulum, e.g. inositol triphosphate receptor channels open in response to InsPs itself and certain other inositol phosphates, are sensitized by thiomersal (which increases the sensitivity of the receptor to InsPs by acting as a sulphydryl reagent) and antagonized by heparin. The various ryanodine receptor channels, at which a putative natural agonist is cyclic adenosine diphosphate ribose (cADP-R), are activated by caffeine and low concentrations of ryanodine (but antagonized by high concentrations of ryanodine and ruthenium red). 

Occurs when a drug effect is antagonized by formation of a complex between the effector drug and another compound e.g., protamine binds to heparin to reverse its actions. 

The vasoconstrictor action of shed blood tested by perfusion of the rabbit ear is markedly decreased by heparin and this was known long before the identification of the vasoconstrictor activity as serotonin (5-hydroxytryp-tamine). Heparin inhibits the release of both 5-hydroxytryptamine and a polypeptide from platelets into plasma, and in vitro there is mutual antagonism between heparin and 5-hydroxytryptamine . Heparin effectively antagonizes the effect of serotonin on pulmonary vascular bed and bronchial wall musculature and prevents the symptoms of 5-HT release in pulmonary embolism, in the cardiopulmonary by-pass, in experimental burn injuries and in carcinoid tumour. 

A number of other synthetic polyanions that bind to the heparin-binding site of FGF (more appropriately perhaps termed the polyanion-binding site) serve not to protect FGF, but rather to antagonize its activity. The most familiar compound of this type is probably suramin, which prevents... 

In vitro studies have revealed that a number of mitogens are released by endothelial cells PDGF-A and -B [280,281], bFGF [282,283], endothelin-1 [284], and connective tissue growth factor [285]. On the other hand, endothelial cells can produce factors that antagonize the SMC proliferation such as heparin [286], and TGFp [287,288], the latter showing either proliferative or inhibitory properties for SMC. 

P.A. Melo, C.L. Ownby, Ability of wedelolactone, heparin, and pani-bromophenacyl bromide to antagonize the myotoxic effects of two cro-taline venoms and their PLA2 myotoxins, Toxicon 37 (1999) 199-215. 

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