Skip to main content Accessibility help
×
Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-23T03:52:34.998Z Has data issue: false hasContentIssue false

Chapter 33 - Cellular Targets of Antiplatelet Agents

from SECTION 3 - MOLECULAR THERAPEUTICS

Published online by Cambridge University Press:  04 June 2019

Nanthakumarn Chetty
Affiliation:
BSc, BSc (Hons), MSc, PhD, Associate Professor, University of the Witwatersrand and National Health Laboratory Service, heads the Platelet Research Unit in the Division of Molecular Medicine and Haematology, School of Pathology, at the University of the Witwatersrand.
Marion Münster
Affiliation:
BSc (Med), MB BCh, DTMH, MMed (Haematology), is Pathologist in Charge, Coagulation Laboratory, Division of Molecular Medicine and Haematology, National Health Laboratory Service and University of the Witwatersrand.
Barry Mendelow
Affiliation:
University of the Witwatersrand, Johannesburg
Michèle Ramsay
Affiliation:
University of the Witwatersrand, Johannesburg
Nanthakumarn Chetty
Affiliation:
University of the Witwatersrand, Johannesburg
Wendy Stevens
Affiliation:
University of the Witwatersrand, Johannesburg
Get access

Summary

INTRODUCTION

Platelets are anuclear and circulate in the bloodstream as discoid, smooth-surfaced cells about 1–3 μm in diameter. They have a circumferential band of microtubules and two membrane systems, the endoplasmic reticulum or dense tubular system and the plasma membrane-derived surface-connected canalicular system. They also contain alpha granules, dense granules, lysosomes and peroxisomes. The alpha granules contain various poly - peptides including fibrinogen, fibronectin and platelet-derived growth factor (PDGF). Dense granules contain adenosine triphosphate (ATP), adenosine diphosphate (ADP) and calcium ions. Platelets play a major role in thrombosis (formation of a blood clot) and haemostasis (arrest of bleeding) after injury.

The platelet membrane has receptors that are poised for immediate interaction with specific adhesive proteins when an area of vascular damage is encountered. These receptors mediate adhesion to subendo thelium, followed by platelet activation, aggregation with other platelets and formation of a firm platelet plug at the site of the vascular leak. When platelets moving along the vessel wall encounter an area of denuded endothelium, they adhere to the subendo thelial matrix, undergo a change in shape to a sphere with multiple pseudopods, and spread to increase their area of surface contact. Agonists in the microenvironment interact with specific receptors on the platelet surface. The agonist-receptor binding transmits signals from outside the cell to the interior, generating second messengers that induce protein phosphorylation and ion channels. As a result, there is activation of the contractile proteins, secretion of granule contents, an increase in adhesion, recruitment of additional platelets by aggregation, thrombus formation and haemostasis.

RECEPTOR-MEDIATED ADHESION

The platelet membrane contains a number of glycoproteins (GPs) that are receptors for adhesive proteins present both in the vessel wall and in plasma. These GPs have been named from GPI to GPIX. The platelet adhesion receptors include GPIa/IIa for colla gen, GPIc/IIa for fibronectin, GPIb for von Willebrand factor (vWF), GPIIb/IIIa fibrin ogen, vWF, fibronectin and vitronectin. The inter action of platelet GPIb with vWF induces intracellular signalling, resulting in a conformational change and activation of the integrin GPIIb/IIIa. vWF then binds irreversibly to the activated GPIIb/IIIa, producing firm adhesion of the platelet to the vessel wall.

Type
Chapter
Information
Publisher: Wits University Press
Print publication year: 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

  • Cellular Targets of Antiplatelet Agents
    • By Nanthakumarn Chetty, BSc, BSc (Hons), MSc, PhD, Associate Professor, University of the Witwatersrand and National Health Laboratory Service, heads the Platelet Research Unit in the Division of Molecular Medicine and Haematology, School of Pathology, at the University of the Witwatersrand., Marion Münster, BSc (Med), MB BCh, DTMH, MMed (Haematology), is Pathologist in Charge, Coagulation Laboratory, Division of Molecular Medicine and Haematology, National Health Laboratory Service and University of the Witwatersrand.
  • Edited by Barry Mendelow, University of the Witwatersrand, Johannesburg, Michèle Ramsay, University of the Witwatersrand, Johannesburg, Nanthakumarn Chetty, University of the Witwatersrand, Johannesburg, Wendy Stevens, University of the Witwatersrand, Johannesburg
  • Book: Molecular Medicine for Clinicians
  • Online publication: 04 June 2019
Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

  • Cellular Targets of Antiplatelet Agents
    • By Nanthakumarn Chetty, BSc, BSc (Hons), MSc, PhD, Associate Professor, University of the Witwatersrand and National Health Laboratory Service, heads the Platelet Research Unit in the Division of Molecular Medicine and Haematology, School of Pathology, at the University of the Witwatersrand., Marion Münster, BSc (Med), MB BCh, DTMH, MMed (Haematology), is Pathologist in Charge, Coagulation Laboratory, Division of Molecular Medicine and Haematology, National Health Laboratory Service and University of the Witwatersrand.
  • Edited by Barry Mendelow, University of the Witwatersrand, Johannesburg, Michèle Ramsay, University of the Witwatersrand, Johannesburg, Nanthakumarn Chetty, University of the Witwatersrand, Johannesburg, Wendy Stevens, University of the Witwatersrand, Johannesburg
  • Book: Molecular Medicine for Clinicians
  • Online publication: 04 June 2019
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Cellular Targets of Antiplatelet Agents
    • By Nanthakumarn Chetty, BSc, BSc (Hons), MSc, PhD, Associate Professor, University of the Witwatersrand and National Health Laboratory Service, heads the Platelet Research Unit in the Division of Molecular Medicine and Haematology, School of Pathology, at the University of the Witwatersrand., Marion Münster, BSc (Med), MB BCh, DTMH, MMed (Haematology), is Pathologist in Charge, Coagulation Laboratory, Division of Molecular Medicine and Haematology, National Health Laboratory Service and University of the Witwatersrand.
  • Edited by Barry Mendelow, University of the Witwatersrand, Johannesburg, Michèle Ramsay, University of the Witwatersrand, Johannesburg, Nanthakumarn Chetty, University of the Witwatersrand, Johannesburg, Wendy Stevens, University of the Witwatersrand, Johannesburg
  • Book: Molecular Medicine for Clinicians
  • Online publication: 04 June 2019
Available formats
×