Characterisation of Human Platelet Adrenoceptors

Barnett, David; Ss, Swart; Nahorski, Stefan R.; Cook, N.

doi:10.1007/978-1-4615-9442-0_8

Cited by 5 publications

(3 citation statements)

References 22 publications

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“…Both serotonin and histamine also induce host sensations of burning and itching that might disturb feeding (28). NE and epinephrine stimulate vasoconstriction, and epinephrine also acts as a platelet agonist (29). Sequestration of these biogenic amines during mosquito feeding would thus serve the important functions of inhibiting platelet aggregation, vasoconstriction, inflammation, and host behavioral responses that might disturb feeding.…”

Section: Resultsmentioning

confidence: 99%

Function and Evolution of a Mosquito Salivary Protein Family

Calvo¹,

Mans²,

Andersen

et al. 2006

Journal of Biological Chemistry

236

299

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Saliva of blood-sucking arthropods contains a complex and diverse mixture of antihemostatic, antiinflammatory, and immunomodulatory compounds. The D7 salivary family of proteins is abundantly expressed in blood-feeding Diptera and is distantly related to the odorant-binding protein superfamily. In mosquitoes, two subfamilies exist, the long and short D7 proteins. Ticks and kissing bugs evolved salivary lipocalins that act as efficient scavengers of biogenic amines, and a similar function was postulated for the D7 proteins. Accordingly, we expressed the five members of the small D7 family of the African malaria vector Anopheles gambiae and a D7 long form from Aedes aegypti and showed by isothermal microcalorimetry, a modified and very sensitive non-equilibrium chromatography/spectrum distortion method, and by smooth muscle bioassay that four of these five short D7 proteins and the D7 long form bind serotonin with high affinity, as well as histamine and norepinephrine. The nonbinding D7 protein is poorly expressed in the salivary glands and appears to be on the path to becoming a pseudogene. Scavenging of host amines would antagonize their vasoconstrictor, platelet-aggregating, and pain-inducing properties. It appears that counteracting biogenic amines is of strong adaptive value in the convergent evolution of arthropods to hematophagy. This adaptation has been solved independently in ticks, bugs, and mosquitoes by co-option of either member of the lipocalin or, as shown here, by the odorant-binding protein families.At least 14 orders or families of arthropods (containing over 400 different genera and more than 15,000 species) independently evolved to feed on vertebrate blood (1). To accomplish this task, these animals evolved sophisticated cocktails of salivary pharmacologic reagents that affect blood clotting, platelet aggregation, vascular contraction, host immunity, inflammation, and angiogenesis. With the development of transcriptome analysis, the salivary compositional diversity of several hematophagous arthropods is being revealed at a fast pace; however, the majority of these proteins have no known function (2).Among many different families of proteins unique to hematophagous arthropods, the D7 family has been recognized to be specifically expressed in the salivary glands of adult Diptera. These proteins are distant relatives of the odorant-binding protein superfamily, of which they are a distinct branch. In mosquitoes, two D7 subfamilies exist, the short family having molecular mass of 15-20 kDa and the long with 27-30 kDa, whereas sand flies appear to have only the long forms (3-5). According to a recent sialotranscriptome analysis, Anopheles gambiae, the main African malaria vector, has three long and five short D7 proteins in chromosome arm 3R (6), arranged in an inverted tandem repeat. In the closely related mosquito Anopheles stephensi, one short D7 protein, named hamadarin, has been expressed and shown to have anticlotting activity (7). No other function has been described for the other protein memb...

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Section: Resultsmentioning

confidence: 99%

Function and Evolution of a Mosquito Salivary Protein Family

Calvo¹,

Mans²,

Andersen

et al. 2006

Journal of Biological Chemistry

236

299

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“…While more than 800 distinct GPCRs exist within the human genome, we noted that PAGln has a somewhat similar structure to catecholamines known to bind to the large multi-gene family of ADRs (Figure 5E). Because ADRs possess a flexible agonist pocket (Masureel et al, 2018), we hypothesized that PAGln may induce cellular signaling through ADRs, focusing on family members present on human platelets (a2A, a2B, and b2 ADRs) (Anfossi and Trovati, 1996;Barnett et al, 1985;Colman, 1990). We initially performed loss-of-function studies in MEG01 cells using both genetic and pharmacological approaches.…”

Section: The Gut Microbiota-dependent Metabolite Pagln Acts Via Adrsmentioning

confidence: 99%

A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors

Nemet

Saha

Gupta

et al. 2020

Cell

496

455

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“…This connection between vascular disease and increased catecholamine levels makes it important to elucidate the impact of catecholamines in thrombus development. Platelets have been shown to express a 2 -adrenergic receptors (a 2 -ARs) and b 2 -ARs [12,13], with a 2 -ARs being 10-20 times more prevalent than b 2 -ARs [12]. Adrenaline can act as a platelet activator by interacting with a 2 -ARs, as evidenced by their sensitivity to the antagonist yohimbine [14].…”

Section: Introductionmentioning

confidence: 98%

Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion

Eriksson

Whiss

Nilsson

2006

Blood Coagulation &Amp; Fibrinolysis

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Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators considered important for thrombus formation, and were previously shown to synergistically increase platelet aggregation. Here we investigate synergistic activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich plasma from healthy blood donors together with adrenaline and/or LPA were added to protein-coated microplates. Platelets were allowed to adhere and the amount of adhesion detected enzymatically. The LPA and adrenaline combination induced a synergistic increase of platelet adhesion to a normally non-adhesive albumin surface. The degree of synergy varied markedly between individuals; these variations could not be explained by age, gender, blood type or different amounts of platelets, oxidized low-density lipoprotein, insulin or glucose in plasma. There was a trend indicating increased synergistic effect for platelets sensitive to adrenaline stimulation. The synergistic effect was blocked by the alpha2-adrenoceptor antagonist yohimbine and inhibited by the ADP scavenger system creatine phosphate/creatine phosphokinase and antibodies against alphaIIbbeta3. Furthermore, platelets adhering to albumin after adrenaline and LPA treatment expressed P-selectin. In conclusion, LPA and adrenaline act synergistically to increase alphaIIbbeta3-mediated platelet adhesion to albumin, dependent on alpha2-adrenoceptor signalling and platelet secretion. We also confirm that synergistic platelet activation achieved with LPA and adrenaline is highly donor dependent.

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Characterisation of Human Platelet Adrenoceptors

Cited by 5 publications

References 22 publications

Function and Evolution of a Mosquito Salivary Protein Family

Function and Evolution of a Mosquito Salivary Protein Family

A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors

Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion

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