English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Effect of phospholipid hydrolysis by phospholipase A2 on the kinetics of antagonist binding to cardiac muscarinic receptors

Rauch, B., Niroomand, F., Messineo, F. C., Weis, A., Kübler, W., & Hasselbach, W. (1994). Effect of phospholipid hydrolysis by phospholipase A2 on the kinetics of antagonist binding to cardiac muscarinic receptors. Biochemical Pharmacology, 48(6), 1289-1296. doi:10.1016/0006-2952(94)90167-8.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0019-A8C6-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-23AD-D
Genre: Journal Article
Alternative Title : Effect of phospholipid hydrolysis by phospholipase A2 on the kinetics of antagonist binding to cardiac muscarinic receptors

Files

show Files
hide Files
:
BiochemPharmacol_48_1994_1289.pdf (Any fulltext), 686KB
 
File Permalink:
-
Name:
BiochemPharmacol_48_1994_1289.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Medical Research, Heidelberg; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Creators

show
hide
 Creators:
Rauch, Bernhard, Author
Niroomand, Feraydoon, Author
Messineo, Frank C., Author
Weis, Angelika, Author
Kübler, Wolfgang, Author
Hasselbach, Wilhelm1, Author              
Affiliations:
1Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_1497712              

Content

show
hide
Free keywords: cardiac muscarinic receptors; phospholipase A2; sarcolemma; quinuclidinyl benzilate; antagonist binding; binding kinetics
 Abstract: Activation of phospholipases during prolonged myocardial ischemia could contribute to the functional derangement of myocardial cells by altering the phospholipid environment of a number of membrane bound proteins including receptors. The present study examined the kinetics of muscarinic receptor antagonist [3H] quinuclidinyl benzilate binding ([3H]QNB) to muscarinic receptors of highly purified sarcolemmal membranes under control conditions and after treatment with phospholipase A2 (PLA2; EC 3.1.1.4.). Initial binding rates of QNB exhibited saturation kinetics, when plotted against the ligand concentration in control and PLA2 treated sarcolemmal membranes. This kinetic behaviour of QNB−binding is consistent with at least a two step binding mechanism. According to this two step binding hypothesis an unstable intermediate receptor−QNB complex (R*QNB) forms rapidly, and this form undergoes a slow conversion to the high affinity ligand−receptor complex R−QNB. The Michaelis constant Km of R−QNB formation was 1.8 nM, whereas the dissociation constant Kd obtained from equilibrium measurements was 0.062 nM. After 5 min exposure of sarcolemmal membranes to PLA2QNB binding capacity (Bmax) was reduced by 62%, and the affinity of the remaining receptor sites was decreased by 47% (Kd = 0.116 nM). This PLA2−induced increase of Kd was accompanied by a corresponding increase of Km, whereas the rate constants k2 and k−2 of the hypothetical slow conversion step (second reaction step) remained unchanged. These results suggest that binding of QNB to cardiac muscarinic receptors induces a transition in the receptor−ligand configuration, which is necessary for the formation of the final high affinity R−QNB complex. PLA2−induced changes of the lipid environment result in the inability of a part of the receptor population to undergo this transition, thereby inhibiting high affinity QNB−binding

Details

show
hide
Language(s): eng - English
 Dates: 1993-07-081994-04-121994-09-15
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Biochemical Pharmacology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Amsterdam, Boston : Elsevier
Pages: - Volume / Issue: 48 (6) Sequence Number: - Start / End Page: 1289 - 1296 Identifier: ISSN: 0006-2952
CoNE: /journals/resource/954925384102