Antihemostatic Molecules from Saliva of Blood-Feeding Arthropods

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Abstract
The ability to feed on vertebrate blood has evolved many times in various arthropod clades. Each time this trait evolves, novel solutions to the problem posed by vertebrate hemostasis are generated. Consequently, saliva of blood-feeding arthropods has proven to be a rich source of antihemostatic molecules. Vasodilators include nitrophorins (nitric oxide storage and transport heme proteins), a variety of peptides that mimic endogenous vasodilatory neuropeptides, and proteins that catabolize or sequester endogenous vasoconstrictors. A variety of platelet aggregation inhibitors antagonize platelet responses to wound-generated signals, including ADP, thrombin, and collagen. Anticoagulants disrupt elements of both the intrinsic and extrinsic pathways. Molecular approaches (termed 'sialomics') to characterize the full inventory of mRNAs transcribed in salivary glands have revealed a surprising level of complexity within a single species. Multiple salivary proteins may be directed against each component of hemostasis, resulting in both redundancy and in some cases cooperative interactions between antihemostatic proteins, as in the case of the Rhodnius prolixus apyrase (which hydrolyzes ADP) and Rhodnius platelet aggregation inhibitor 1 (which sequesters ADP). The complexity and redundancy of saliva ensures an efficient blood meal for the arthropod, but it also provides a diverse array of novel antihemostatic molecules for the pharmacologist.