Activation of the IP3 receptor
on the endoplasmic reticulum releases calcium into the cytosolic compartment .
We show here, for the first time, that in platelet-rich plasma CLA blocked clot retraction and inhibited cytosolic [Ca.sup.2+] elevation upstream of the IP3 receptor, abolished PS-expression, and subsequently inhibited thrombin generation.
By using thiomersal, a direct activator of the intracellular IP3 receptors, we could verify both by flow cytometric PSexpression studies and by the ratiometric calcium measurement that PP inhibition by CLA does not impair direct IP3 receptor stimulation, so its effect is exerted upstream of the IP3 receptor.
Since 1997, we were studying 2-aminoethyl diphenylborinate (2-APB) analogues to find IP3 receptor
inhibitor and regulate IP3-induced calcium release [106-128].
In the case of relaxation of arterial smooth muscle, (1) muscarinic [M.sub.3] receptors in endothelial cells respond to ACh and initiate the signal transduction leading to formation of NO (nitric oxide) through many steps including Gq, phospholipase C[beta]1, IP3 receptor
, [Ca.sup.2+] /calmodulin, and NO synthase, (2) NO diffuses into smooth muscle and there activates NO receptor with guanylate cyclase activity, and (3) cGMP activates protein kinase G which leads to relaxation of the muscle and then vasodilation (see a review ref.
IP3 is used for signal transduction in biological cells via the release of calcium from the endoplasmic reticulum via the IP3 receptor
This is important, Montminy says, because the team also discovered that activity of the IP3 receptor
and calcineurin in the liver are increased in diabetic insulin resistance, resulting in more blood sugar.
IP3 induces [Ca.sup.2+] release from the intracellular endoplasmic reticulum through IP3 receptor
, (36) and [Ca.sup.2+] and diacylglycerol synergistically activate protein kinase C (PKC)37) (Fig.
Mechanisms for the regulation of LPS-induced TLR4 endocytosis and IRF3 activation by PLC[gamma]-2 have been established: IP3, the cleavage product of PI(4,5)P2 by PLC[gamma]-2, binding to IP3 receptors
(IP3Rs) in the endoplasmic reticulum results in the release of [Ca2.sup.+].
Yuan et al., "Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors
," Neuron, vol.
The results in our study, however, have not identified a specific site for the inhibitory action of schisandrin A, for example, the phospholipase C or (and) IP3 receptors