Inotropic action of σ receptor ligands in isolated cardiac myocytes from adult rats

Marie Novakova, Catherine Ela, Jacob Barg, Zvi Vogel, Yonathan Hasin, Yael Eilam

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Abstract

High affinity binding sites for σ receptor ligands were found in membranes of cardiac myocytes from adult rats. The σ receptor ligand (+)-3-hydroxyphenyl-N-(1-propyl)piperidine ((+)-3-PPP) binds with a Kd of 17.9 ± 4.0 nM and a Bmax of 275 ± 32.1 fmol/mg protein. Competition experiments of (+)-pentazocine with [3H]1,3-di-O-tolylguanidine ([3H]DTG) binding yielded a Ki of 6.1 ± 1.3 nM. The majority of the sites (> 80%) were of the σ1 subtype. Exposure of isolated cardiomyocytes from adult rats to (+)-3-PPP (10 nM-1.0 μM) caused a marked concentration-dependent increase in the amplitude of systolic cell contraction, reaching 149% of control level, with an apparent ED50 value of 4.5 nM. The increase in the contraction amplitude was markedly inhibited by pretreatment with verapamil or thapsigargin. An increase in the amplitude of [Ca2+]i transients, similar to that in the amplitude of cell contraction, was observed in indo-1-loaded cardiomyocytes exposed to 0.1 μM (+)-3-PPP. Exposure to 10 nM of haloperidol or (+)-pentazocine induced an increase in the amplitude of contraction, reaching 188% and 138% (respectively) of control level. A lower concentration of haloperidol or (+)-pentazocine (1 nM) did not induce an increase in the contraction amplitude but rather reduced the amplitude to 70-80% of control.

Original languageEnglish
Pages (from-to)19-30
Number of pages12
JournalEuropean Journal of Pharmacology
Volume286
Issue number1
DOIs
StatePublished - 3 Nov 1995
Externally publishedYes

Bibliographical note

Funding Information:
This researchw as supportedb y a grant from the Chief Scientisto f the Ministry of Health, Israel (to Y.E.) and by a grant from the Israel-USA Binational Foundation(t o Z.V. and J.B.).

Funding

This researchw as supportedb y a grant from the Chief Scientisto f the Ministry of Health, Israel (to Y.E.) and by a grant from the Israel-USA Binational Foundation(t o Z.V. and J.B.).

FundersFunder number
Israel-USA Binational Foundation
Ministry of Health, State of Israel

    Keywords

    • Cardiac myocyte
    • Contractility
    • [Ca] transient
    • σ Receptor

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