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You searched for subject:(PAR1 agonist). Showing records 1 – 2 of 2 total matches.

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Temple University

1. Mao, Yingying. ROLE OF PROTEASE-ACTIVATED RECEPTORS IN PLATELET ACTIVATION.

Degree: PhD, 2009, Temple University

Physiology

Platelets act as a fundamental component of the hemostatic process and their activation leads to the formation of a stable clot at the injured endothelium surface. Thrombin, as the important physiological agonist, activates platelets through protease-activated receptors (PARs). Protease-activated receptors are one of the major receptors in platelets and belong to the seven-transmembrane G-protein couple receptor family. Four protease-activated receptors are found, named as PAR1, PAR2, PAR3 and PAR4. Human platelets express PAR1 and PAR4 and murine platelets express PAR4 and PAR3 instead of PAR1. Thrombin activates PARs through a unique mechanism, involving the cleavage of N-terminus of PAR receptors and the newly exposed N-terminus acts as its own tethered ligand to bind and activate the receptor. In this study, we characterized a new PAR1 specific activating peptide (TFRRRLSRATR), generated from the c-terminus of human platelet P2Y1 receptor, and evaluated its biological function. This peptide activated platelets in a concentration-dependent manner, causing shape change, aggregation, secretion and calcium mobilization. Its activation is completely inhibited by using BMS200261, a PAR-1 specific antagonist. Its specificity to PAR1 receptor is further confirmed by using TFRRR-peptide-pretreated washed platelets and murine platelets. The shape change induced by 10 microM peptide was totally abolished by Y-27632, an inhibitor of p160ROCK which is the downstream signal of G12/13 pathways. The TFRRR-peptide, YFLLRNP, and the physiological agonist thrombin selectively activated G12/13 pathways at low concentrations and began to activate both Gq and G12/13 pathways with increased concentrations. Similar to SFLLRN, the TFRRR-peptide caused phosphorylation of Akt and Erk in a P2Y12 receptor-dependent manner, and p-38 MAP kinase activation in a P2Y12-independent manner. The effects of this peptide are elicited by the first six amino acids (TFRRRL) whereas the remaining peptide (LSRATR), TFERRN, or TFEERN had no effects on platelets. Beside thrombin, PARs also can be activated by other proteases. Previous studies in our lab show that plasmin, a major extracellular protease, activates both human and murine platelets through prototypical cleavage of PAR4 (Quinton et al., 2004). In this study, we continue our study and investigate the molecular basis for the differential activation of murine and human platelets by plasmin. Plasmin-induced full aggregation is achieved at lower concentrations (0.1 U/mL) in murine platelets as compared to human platelets (1 U/mL). In COS7 cells expressing the murine PAR4 (mPAR4) receptor, 1 U/mL plasmin caused a higher intracellular calcium mobilization than in cells expressing the human PAR4 (hPAR4) receptor. This difference was reversed when the tethered ligand sequences of mPAR4 and hPAR4 were interchanged through site-directed mutagenesis. This difference between human and murine PAR4 is not because of the cofactor effect of PAR3 in murine platelets by…

Advisors/Committee Members: Kunapuli, Satya P., Daniel, James L., Tuma, Ronald F. (Ronald Franklin), Autieri, Michael V., Driska, Steven Paul, Woulfe, Donna.

Subjects/Keywords: Biology, Physiology; ischemic injury; PAR1 agonist; plasmin; platelet; protease-activated receptor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Mao, Y. (2009). ROLE OF PROTEASE-ACTIVATED RECEPTORS IN PLATELET ACTIVATION. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,47279

Chicago Manual of Style (16th Edition):

Mao, Yingying. “ROLE OF PROTEASE-ACTIVATED RECEPTORS IN PLATELET ACTIVATION.” 2009. Doctoral Dissertation, Temple University. Accessed October 22, 2020. http://digital.library.temple.edu/u?/p245801coll10,47279.

MLA Handbook (7th Edition):

Mao, Yingying. “ROLE OF PROTEASE-ACTIVATED RECEPTORS IN PLATELET ACTIVATION.” 2009. Web. 22 Oct 2020.

Vancouver:

Mao Y. ROLE OF PROTEASE-ACTIVATED RECEPTORS IN PLATELET ACTIVATION. [Internet] [Doctoral dissertation]. Temple University; 2009. [cited 2020 Oct 22]. Available from: http://digital.library.temple.edu/u?/p245801coll10,47279.

Council of Science Editors:

Mao Y. ROLE OF PROTEASE-ACTIVATED RECEPTORS IN PLATELET ACTIVATION. [Doctoral Dissertation]. Temple University; 2009. Available from: http://digital.library.temple.edu/u?/p245801coll10,47279


University of St. Andrews

2. Acton, David. Regulation of mammalian spinal locomotor networks by glial cells .

Degree: 2017, University of St. Andrews

Networks of interneurons within the spinal cord coordinate the rhythmic activation of muscles during locomotion. These networks are subject to extensive neuromodulation, ensuring appropriate behavioural output. Astrocytes are proposed to detect neuronal activity via Gαq-linked G-protein coupled receptors and to secrete neuromodulators in response. However, there is currently a paucity of evidence that astrocytic information processing of this kind is important in behaviour. Here, it is shown that protease-activated receptor-1 (PAR1), a Gαq-linked receptor, is preferentially expressed by glia in the spinal cords of postnatal mice. During ongoing locomotor-related network activity in isolated spinal cords, PAR1 activation stimulates release of adenosine triphosphate (ATP), which is hydrolysed to adenosine extracellularly. Adenosine then activates A1 receptors to reduce the frequency of locomotor-related bursting recorded from ventral roots. This entails inhibition of D1 dopamine receptors, activation of which enhances burst frequency. The effect of A1 blockade scales with network activity, consistent with activity-dependent production of adenosine by glia. Astrocytes also regulate activity by controlling the availability of D-serine or glycine, both of which act as co-agonists of glutamate at N-methyl-D-aspartate receptors (NMDARs). The importance of NMDAR regulation for locomotor-related activity is demonstrated by blockade of NMDARs, which reduces burst frequency and amplitude. Bath-applied D-serine increases the frequency of locomotor-related bursting but not intense synchronous bursting produced by blockade of inhibitory transmission, implying activity-dependent regulation of co-agonist availability. Depletion of endogenous D-serine increases the frequency of locomotor-related but not synchronous bursting, indicating that D-serine is required at a subset of NMDARs expressed by inhibitory interneurons. Blockade of the astrocytic glycine transporter GlyT1 increases the frequency of locomotor-related activity, but application of glycine has no effect, indicating that GlyT1 regulates glycine at excitatory synapses. These results indicate that glia play an important role in regulating the output of spinal locomotor networks. Advisors/Committee Members: Miles, Gareth Brian (advisor).

Subjects/Keywords: Spinal cord physiology; Locomotion; Central pattern generator; CPG; Motor control; NMDA receptors; Glia; Glial cells; Astrocytes; Neural networks; Gliotransmission; PAR1; Dopamine; Co-agonist; D-serine; Glycine; GlyT1

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Acton, D. (2017). Regulation of mammalian spinal locomotor networks by glial cells . (Thesis). University of St. Andrews. Retrieved from http://hdl.handle.net/10023/10133

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Acton, David. “Regulation of mammalian spinal locomotor networks by glial cells .” 2017. Thesis, University of St. Andrews. Accessed October 22, 2020. http://hdl.handle.net/10023/10133.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Acton, David. “Regulation of mammalian spinal locomotor networks by glial cells .” 2017. Web. 22 Oct 2020.

Vancouver:

Acton D. Regulation of mammalian spinal locomotor networks by glial cells . [Internet] [Thesis]. University of St. Andrews; 2017. [cited 2020 Oct 22]. Available from: http://hdl.handle.net/10023/10133.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Acton D. Regulation of mammalian spinal locomotor networks by glial cells . [Thesis]. University of St. Andrews; 2017. Available from: http://hdl.handle.net/10023/10133

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.