Platelet aggregating activity of lysophosphatidic acids is not related to their calcium ionophore properties

AbstractThe calcium ionophore properties of A23187 and of two lysophosphatidic acid (LPA) analogs (1-palmitoyl- and 1-hexadecyl-sn-glycero-3-phosphate or P-GPA and H-GPA, respectively) were compared using platelet membrane vesicles loaded with 45Ca. Half maximal effect (HME) was obtained at 5 μM and 10 μM for H-GPA and P-GPA, respectively, against 0.7 μM for A23187, which released 2 times more Ca. The three compounds also induced platelet aggregation with a HME at 0.5 μM, 0.3 μM and 0.01 μM for A23187, P-GPA and H-GPA, respectively. The clear dissociation between the two effects appearing for both LPA raises some doubt about the general idea that (lyso) PA participate in cell activation through their calcium ionophore properties

αIIbβ3-integrin mediated adhesion of human platelets to a fibrinogen matrix triggers phospholipase C activation and phosphatidylinositol 3′,4′-bisphosphate accumulation

AbstractThis study focused on the variations in phosphoinositide metabolism depending upon αIIbβ3-integrin/fibrinogen interaction without previous activation of platelet agonist receptors. We found that adhesion of resting human platelets to immobilized fibrinogen stimulates phosphatidic acid production and a concomitant decrease in phosphatidylinositol 4′,5′-bisphosphate. These results, and the absence of a transphosphatidylation reaction, argue in favor of the activation of a phospholipase C. Moreover, we observed the accumulation of phosphatidylinositol 3′,4′-bisphosphate in adherent platelets as a consequence of the activation of a phosphatidylinositol 3-kinase. This effect was inhibited by ADP scavengers. Our results demonstrate that in adherent platelets, whereas phosphatidylinositol 3-kinase activation is controlled by both αIIbβ-integrin engagement and released ADP, phospholipase C stimulation is triggered only by αIIbβ-integrin/fibrinogen interaction

Etude des effets cutanés de l'hormone de croissance chez l'homme

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Des ITIM du lymphocyte aux integrines de la plaquette: SHIP, une proteine a la croisee des chemins?

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

pp60(c-src) associates with the SH2-containing inositol-5-phosphatase SHIP1 and is involved in its tyrosine phosphorylation downstream of αIIbβ3 integrin in human platelets

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Possible Role of Adipose Tissue and the Endocannabinoid System in Coronavirus Disease 2019 Pathogenesis: Can Rimonabant Return?

International audienceThis is the main conclusion of a recent study describing a strong relationship between the degree of obesity and the severity of COVID‐19 infection. Obesity has various negative consequences relative to the course of COVID‐19, including adverse effects on lung physiology, and induces comorbidities such as type II diabetes or hypertension. However, additional mechanisms involving the low‐grade inflammatory state accompanying obesity can also be suggeste

Can antidepressants unlock prescription of rimonabant in the fight against COVID-19?

International audienceWe read with real enthusiasm the paper by Hoertel et al. showing an “association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19”. Their observation reinforces preliminary data of a double-blind, randomized clinical trial showing significant reduction of COVID-19 worsening in outpatients treated with fluvoxamine. By the time those promising results should obviously stimulate organization of large randomized clinical trials on the use of antidepressants in the fight against COVID-19, we want to plead for introducing rimonabant combined to an antidepressant in some of those trials as well as in preclinical studies