Growth Hormones Reverse Desensitization of P2Y2 Receptors in Rat Mesangial Cells

Purinergic modulation of mesangial extracellular matrix production: Role in diabetic and other glomerular diseases

“…Recent evidence suggests a link between PKC and the purinergic system. In fact, PKC activation was shown to induce desensitization of P2Y 2 in rat mesangial cells [55], that is in keeping with our finding of a down-regulatory effect of P2YRs on mesangial matrix production. Moreover, stimulation of rat mesangial cells with ATP and UTP leads to a rapid activation of the PKB pathway, a cascade known to play an important role in the antiapoptotic, but not inflammatory or mitogenic response [56].…”

Resensitization of P2Y Receptors by Growth Factor–Mediated Activation of the Phosphatidylinositol-3 Kinase in Retinal Glial Cells

“…In other cell systems, activation of PKC has been found to be essential for growth factor-induced P2Y receptor resensitization. 23,24 Moreover, a blocking effect of okadaic acid on P2Y 2 receptor resensitization has been observed in several different cell systems. 32,35 The activation of both PI3K and protein phosphatases may result in alterations of the functional state of the receptors or of the functional coupling of the receptors to the calcium signaling pathway.…”

“…23,24 Because growth factors have been crucially implicated in the retinal responses during detachment and PVR, 5,18,19 we investigated the effects of EGF, PDGF, and NGF on the ATP-induced desensitization of P2Y receptors in Müller cells. EGF (in a concentration range between 50 and 200 ng/mL) evoked transient calcium responses in 50% to 70% of the cells investigated, with a maximum effect at 100 ng/mL (Figs.…”

Coupling of P2Y receptors to G proteins and other signaling pathways

“…Activation of receptor tyrosine kinases by growth factors has been shown to resensitize P2Y receptors in many different cell types by PKC‐dependent P2Y receptor phosphorylation 87,88. In retinal glial cells, P2Y receptors are desensitized by ATP and resensitized by growth factors (e.g., EGF, PDGF, NGF), via activation of PI3K and protein phosphatases, whereas resensitization is not dependent on the activity of PKC, Src kinases, or ERK1/2 89…”