Inhibition of the positive inotropic effect of anthopleurin-A (AP-A) by dantrolene

Leslie E. Bailey; Shoji Shibata; David G. Seriguchi; Peter E. Dresel

doi:10.1016/0024-3205(80)90252-0

Inhibition of the positive inotropic effect of anthopleurin-A (AP-A) by dantrolene

Leslie E. Bailey, Shoji Shibata, David G. Seriguchi, Peter E. Dresel

Medicine

Medicine

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

The effect of dantrolene on the positive inotropic effects (PIE) of three cardiotonic agents was assessed on rat and rabbit atria. Dantrolene (10^-5M) had no effect on contractile tension or on the PIE to isoproterenol (10^-10-10^-7M) or ouabain (10^-6-10^-4). The dose-response curve for the PIE of anthopleurin-A (AP-A) was shifted to the right in rat and rabbit atria by dantrolene (10^-4-10^-6M). The maximum effect and the concentration of AP-A required for it remained the same. The results suggest that the PIE of AP-A involves intracellular translocation of calcium, unlike those of isoproterenol and ouabain which require increased transmembrane calcium flux. This conclusion is supported by the observation that the exchange and distribution of the labile calcium involved in excitation-contraction coupling was unaffected by AP-A (10^-8M), by dantrolene (10^-6M) or by the combination. Therefore, AP-A may produce its cardiotonic effect by a action at an intracellular site, a mechanism unlike that of isoproterenol or ouabain.

Original language	English
Pages (from-to)	1061-1068
Number of pages	8
Journal	Life Sciences
Volume	26
Issue number	13
DOIs	https://doi.org/10.1016/0024-3205(80)90252-0
Publication status	Published - Mar 31 1980

Bibliographical note

Funding Information:
Anthopleurin-A (AP-A) is a potent cardiostimulant polypeptide containing 49 amino acids (molecular weight ~ 5195) isolated from Isupported by Medical Research Council of Canada Grant MA-4250 and the Nova Scotia Heart Foundation. Presented in part at the Federation of American Societies for Experimental Biology, Atlantic City, N.J., April, 1978. 2Address editorial comments and reprint request to Dr. L.E. Bailey at the above address. 3The work was done during Dr. Shibata's tenure as a Visiting Scientist of the Canadian Heart Foundation. Present address: Department of Pharmacology, University of Hawaii, Honolulu, HI.

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology
Pharmacology, Toxicology and Pharmaceutics(all)

Access to Document

10.1016/0024-3205(80)90252-0

Cite this

@article{b3100f1a364548f2b06ea21aa08a3705,

title = "Inhibition of the positive inotropic effect of anthopleurin-A (AP-A) by dantrolene",

abstract = "The effect of dantrolene on the positive inotropic effects (PIE) of three cardiotonic agents was assessed on rat and rabbit atria. Dantrolene (10-5M) had no effect on contractile tension or on the PIE to isoproterenol (10-10-10-7M) or ouabain (10-6-10-4). The dose-response curve for the PIE of anthopleurin-A (AP-A) was shifted to the right in rat and rabbit atria by dantrolene (10-4-10-6M). The maximum effect and the concentration of AP-A required for it remained the same. The results suggest that the PIE of AP-A involves intracellular translocation of calcium, unlike those of isoproterenol and ouabain which require increased transmembrane calcium flux. This conclusion is supported by the observation that the exchange and distribution of the labile calcium involved in excitation-contraction coupling was unaffected by AP-A (10-8M), by dantrolene (10-6M) or by the combination. Therefore, AP-A may produce its cardiotonic effect by a action at an intracellular site, a mechanism unlike that of isoproterenol or ouabain.",

author = "Bailey, {Leslie E.} and Shoji Shibata and Seriguchi, {David G.} and Dresel, {Peter E.}",

note = "Funding Information: Anthopleurin-A (AP-A) is a potent cardiostimulant polypeptide containing 49 amino acids (molecular weight ~ 5195) isolated from Isupported by Medical Research Council of Canada Grant MA-4250 and the Nova Scotia Heart Foundation. Presented in part at the Federation of American Societies for Experimental Biology, Atlantic City, N.J., April, 1978. 2Address editorial comments and reprint request to Dr. L.E. Bailey at the above address. 3The work was done during Dr. Shibata's tenure as a Visiting Scientist of the Canadian Heart Foundation. Present address: Department of Pharmacology, University of Hawaii, Honolulu, HI.",

year = "1980",

month = mar,

day = "31",

doi = "10.1016/0024-3205(80)90252-0",

language = "English",

volume = "26",

pages = "1061--1068",

journal = "Life Sciences",

issn = "0024-3205",

publisher = "Elsevier Inc.",

number = "13",

}

TY - JOUR

T1 - Inhibition of the positive inotropic effect of anthopleurin-A (AP-A) by dantrolene

AU - Bailey, Leslie E.

AU - Shibata, Shoji

AU - Seriguchi, David G.

AU - Dresel, Peter E.

N1 - Funding Information: Anthopleurin-A (AP-A) is a potent cardiostimulant polypeptide containing 49 amino acids (molecular weight ~ 5195) isolated from Isupported by Medical Research Council of Canada Grant MA-4250 and the Nova Scotia Heart Foundation. Presented in part at the Federation of American Societies for Experimental Biology, Atlantic City, N.J., April, 1978. 2Address editorial comments and reprint request to Dr. L.E. Bailey at the above address. 3The work was done during Dr. Shibata's tenure as a Visiting Scientist of the Canadian Heart Foundation. Present address: Department of Pharmacology, University of Hawaii, Honolulu, HI.

PY - 1980/3/31

Y1 - 1980/3/31

N2 - The effect of dantrolene on the positive inotropic effects (PIE) of three cardiotonic agents was assessed on rat and rabbit atria. Dantrolene (10-5M) had no effect on contractile tension or on the PIE to isoproterenol (10-10-10-7M) or ouabain (10-6-10-4). The dose-response curve for the PIE of anthopleurin-A (AP-A) was shifted to the right in rat and rabbit atria by dantrolene (10-4-10-6M). The maximum effect and the concentration of AP-A required for it remained the same. The results suggest that the PIE of AP-A involves intracellular translocation of calcium, unlike those of isoproterenol and ouabain which require increased transmembrane calcium flux. This conclusion is supported by the observation that the exchange and distribution of the labile calcium involved in excitation-contraction coupling was unaffected by AP-A (10-8M), by dantrolene (10-6M) or by the combination. Therefore, AP-A may produce its cardiotonic effect by a action at an intracellular site, a mechanism unlike that of isoproterenol or ouabain.

AB - The effect of dantrolene on the positive inotropic effects (PIE) of three cardiotonic agents was assessed on rat and rabbit atria. Dantrolene (10-5M) had no effect on contractile tension or on the PIE to isoproterenol (10-10-10-7M) or ouabain (10-6-10-4). The dose-response curve for the PIE of anthopleurin-A (AP-A) was shifted to the right in rat and rabbit atria by dantrolene (10-4-10-6M). The maximum effect and the concentration of AP-A required for it remained the same. The results suggest that the PIE of AP-A involves intracellular translocation of calcium, unlike those of isoproterenol and ouabain which require increased transmembrane calcium flux. This conclusion is supported by the observation that the exchange and distribution of the labile calcium involved in excitation-contraction coupling was unaffected by AP-A (10-8M), by dantrolene (10-6M) or by the combination. Therefore, AP-A may produce its cardiotonic effect by a action at an intracellular site, a mechanism unlike that of isoproterenol or ouabain.

UR - http://www.scopus.com/inward/record.url?scp=0018831360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018831360&partnerID=8YFLogxK

U2 - 10.1016/0024-3205(80)90252-0

DO - 10.1016/0024-3205(80)90252-0

M3 - Article

C2 - 7392786

AN - SCOPUS:0018831360

SN - 0024-3205

VL - 26

SP - 1061

EP - 1068

JO - Life Sciences

JF - Life Sciences

IS - 13

ER -

Inhibition of the positive inotropic effect of anthopleurin-A (AP-A) by dantrolene

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Access to Document

Other files and links

Fingerprint

Cite this