St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • Biology (School of)
  • Biology
  • Biology Theses
  • View Item
  •   St Andrews Research Repository
  • Biology (School of)
  • Biology
  • Biology Theses
  • View Item
  •   St Andrews Research Repository
  • Biology (School of)
  • Biology
  • Biology Theses
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

Atrial natriuretic peptide receptor subtype determination and biological actions of atrial natriuetic peptided in bovine cardiac muscle and hypertensive rat liver

Thumbnail
View/Open
ShirleyMcCartneyPhDThesis.pdf (31.51Mb)
Date
1992
Author
McCartney, Shirley
Supervisor
Cramb, Gordon
Aiton, Jim
Funder
British Heart Foundation
Maitland Ramsay studentship fund
Metadata
Show full item record
Altmetrics Handle Statistics
Abstract
Atrial natriuretic peptide (ANP) has previously been shown to bind to specific ANP receptors and increase intracellular cGMP levels in purified rat cardiac sarcolemmal membranes. Experiments described in this thesis were performed to investigate the binding characteristics of ANP in bovine ventricular sarcolemmal membranes and in plasma membranes isolated from the liver of hypertension-resistant and hypertension-sensitive Dahl rats fed on two dietary salt regimes one of 0.8% NaCl and the other 8% NaCl. Additional experiments utilising ANP analogues in radio-receptor assays and radio-receptor crosslinking assays were performed to determine the precise nature of the ANP receptor population present in these membrane preparations. In bovine ventricular cardiac sarcolemmal membranes, ANP bound specifically to one class of ANP receptor with a Kd of approximately 44 pM and a Bmax of approximately 49 fmol/mg protein. ANP produced a 1.8-fold stimulation of manganese-dependent guanylate cyclase activity with an EC50 value of approximately 1 nM. Receptor binding using the des-ANP analogue indicated the predominant presence of the ANP-B receptor subtype. Radioreceptor crosslinking experiments did not entirely agree with these experiments. Radio-receptor crosslinking indicated the presence of two ANP receptors one of 60 kDa and one of 120 kDa, equivalent to the molecular weights of ANP receptors found in other tissues. Collectively these experiments indicate that bovine ventricular sarcolemmal membranes possess ANP receptors, at least a proportion of which are coupled to guanylate cyclase (ANP-B receptors). In plasma membranes from the liver of Dahl-Resistant (Dahl-R) and Dahl-Sensitive (Dahl-S) rats, ANP bound specifically to one class of ANP receptor with Kd values ranging from 245 to 288 pM and Bmax values ranging from 104 to 217 fmol/mg protein. ANP produced a 3.8 to 6.15-fold stimulation of manganese-dependent guanylate cyclase activity with an EC50 values ranging from 2.3 to 7.4 nM, dependent on the strain of Dahl rat and the dietary salt regime used. In liver membranes isolated from rats sensitive to salt-induced hypertension results indicated increases in Bmax with no change in Kd for ANP binding to receptors and higher basal and ANP-stimulated guanylate cyclase levels. Receptor binding using the des-ANP analogue indicated the presence of 13-33% ANP-C receptors with a majority of ANP-B receptors in plasma membranes isolated from the liver of Dahl-R and Dahl-S rats. However, radio-receptor crosslinking experiments were unable to support these results. Collectively these experiments indicate that in plasma membranes isolated from the liver of Dahl-R and Dahl-S rats possess ANP receptors, at least a majority of which are coupled to guanylate cyclase (ANP-B receptors) and that sensitivity to hypertension induced by a high salt dietary regime increases the density of ANP receptors coupled to guanylate cyclase.
Type
Thesis, PhD Doctor of Philosophy
Collections
  • Biology Theses
URI
http://hdl.handle.net/10023/14455

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter