Modification of the VerifyNow® P2Y12 test BASE channel to accommodate high levels of P2Y(12) antagonism.
Summary of "Modification of the VerifyNow® P2Y12 test BASE channel to accommodate high levels of P2Y(12) antagonism."
The VerifyNow® P2Y12 (VN-P2Y12) test reports thienopyridine-mediated platelet inhibition relative to a "BASE" channel, potentially eliminating the need for predrug patient assessment, by activating platelets through a P2Y(12)-independent pathway. The original formulation of the BASE channel used a protease activated receptor-1 (PAR-1) peptide as agonist. However, more potent P2Y(12) antagonism required more complete activation of platelet thrombin receptors for the BASE measurement in order to negate any contribution of the P2Y(12) receptor. Accordingly, the current BASE channel formulation consists of both PAR-1 and protease activated receptor-4 (PAR-4) activating peptides to facilitate a higher degree of platelet activation. The aim of this study was to compare the performance of PAR-1 versus PAR-1/PAR-4 activating peptides as the BASE channel formulation using prasugrel's active metabolite, R-138727, in vitro to achieve high-grade P2Y(12) inhibition. Blood samples from 20 healthy donors were spiked in vitro with R-138727 at concentrations that include plasma levels achieved following prasugrel administration and were incubated for 30 minutes at 37°C. All samples were run in triplicate using both the PAR-1 and the PAR-1/PAR-4 BASE formulation in the VN-P2Y12 test device. The data confirmed the sensitivity of the original BASE formulation to high-grade P2Y(12) inhibition as reflected in the concentration-dependent decrease in values. Incorporation of PAR-4 activating peptide eliminated the effect of P2Y(12) blockade at all concentrations of R-138727. Thus, the use of PAR-1/PAR-4 in the BASE channel of the VN-P2Y12 cartridge addresses the impact of high grade P2Y(12) blockade and may allow more accurate reporting of "% inhibition" in patients treated with more effective P2Y(12) antagonists.
Lilly Research Laboratories, Eli Lilly and Company , Indianapolis, IN , USA.
This article was published in the following journal.
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21639823
- DOI: http://dx.doi.org/10.3109/09537104.2011.579203
Medical and Biotech [MESH] Definitions
Receptors, Purinergic P2y12
A subclass of purinergic P2Y receptors that have a preference for ADP binding and are coupled to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI. The P2Y12 purinergic receptors are found in PLATELETS where they play an important role regulating PLATELET ACTIVATION.
A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.
Dna Modification Methylases
Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms.
Various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons; vehicles for medicinal substances intended for external application; there are four classes: hydrocarbon base, absorption base, water-removable base and water-soluble base; several are also emollients.
Kcnq3 Potassium Channel
A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is closely related to KCNQ2 POTASSIUM CHANNEL. It is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.
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