The inotropic activity of digitalis genins is dependent upon C(17) side-group carbonyl oxygen position

Arthur H.L. From; Dwight S. Fullerton; Tamboue Deffo; Eitaro Kitatsuji; Douglas C. Rohrer; Khalil Ahmed

doi:10.1016/S0022-2828(84)80007-3

The inotropic activity of digitalis genins is dependent upon C(17) side-group carbonyl oxygen position

Arthur H.L. From, Dwight S. Fullerton, Tamboue Deffo, Eitaro Kitatsuji, Douglas C. Rohrer, Khalil Ahmed

Laboratory Medicine and Pathology

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

10 Scopus citations

Abstract

The inotropic potencies of four digitalis genins were studied utilizing cat left atrial strips. The genin concentration required to induce a 50% increase of isometric tension (T₅₀) was found to closely correlate with the degree of displacement (D) of the C(17) side-group carbonyl oxygen from the position of that atom in digitoxigenin. The line of regression was: log T₅₀=0.54D-6.85, r²=0.98, P0.008. These observations were related to recently reported cat ventricular Na⁺, K⁺-ATPase inhibitory potencies of the same genins [expressed as 50% inhibitory (I₅₀) concentrations]. I₅₀ correlated strongly with T₅₀: log I₅₀=0.78 log T₅₀-1.68, r²=0.99, P0.003. Thus, the activity of digitalis genins towards their receptor in intact cardiac tissue is closely related to genin carbonyl oxygen position as well as to Na⁺, K⁺-ATPase inhibitory activity. These results further support our earlier conclusions, based upon isolated Na⁺, K⁺-ATPase studies, that the digitalis genin C(17) side-group carbonyl oxygen position versus activity relationship is biologically relevant and may prove to be a useful unifying structural model in the further elucidation of the mechanism of digitalis-receptor interactions.

Original language	English (US)
Pages (from-to)	835-842
Number of pages	8
Journal	Journal of Molecular and Cellular Cardiology
Volume	16
Issue number	9
DOIs	https://doi.org/10.1016/S0022-2828(84)80007-3
State	Published - Sep 1984

Bibliographical note

Funding Information:
This research was supported by the National Institutes of Health, DHHS (Grant HL 21457), and the Veterans Administration Medical Research Fund. The organization and analysis of the data base associated with this investigation were carried out in part with the use of the PROPHET system, a unique national resource sponsored by the NIH. Information about PROPHET, including how to apply for access, can be obtained from the Director, Chemical/Biological Information-Handling Program, Division of Research Resources, NIH, Bethesda, MD 20205. The technical assistance of the late Mr Fred Andrews and Mr Michael Barone and skillful manuscript preparation by Ms Mary Bougetz are gratefully acknowledged.

Keywords

C(17) side-group carbonyl oxygen position
Digitalis genins
Inotropism

Access

10.1016/S0022-2828(84)80007-3

OpenUrl availability

Full text

Cite this

@article{4379e363671242f287f0910014d4f538,

title = "The inotropic activity of digitalis genins is dependent upon C(17) side-group carbonyl oxygen position",

abstract = "The inotropic potencies of four digitalis genins were studied utilizing cat left atrial strips. The genin concentration required to induce a 50% increase of isometric tension (T50) was found to closely correlate with the degree of displacement (D) of the C(17) side-group carbonyl oxygen from the position of that atom in digitoxigenin. The line of regression was: log T50=0.54D-6.85, r2=0.98, P0.008. These observations were related to recently reported cat ventricular Na+, K+-ATPase inhibitory potencies of the same genins [expressed as 50% inhibitory (I50) concentrations]. I50 correlated strongly with T50: log I50=0.78 log T50-1.68, r2=0.99, P0.003. Thus, the activity of digitalis genins towards their receptor in intact cardiac tissue is closely related to genin carbonyl oxygen position as well as to Na+, K+-ATPase inhibitory activity. These results further support our earlier conclusions, based upon isolated Na+, K+-ATPase studies, that the digitalis genin C(17) side-group carbonyl oxygen position versus activity relationship is biologically relevant and may prove to be a useful unifying structural model in the further elucidation of the mechanism of digitalis-receptor interactions.",

keywords = "C(17) side-group carbonyl oxygen position, Digitalis genins, Inotropism",

author = "From, {Arthur H.L.} and Fullerton, {Dwight S.} and Tamboue Deffo and Eitaro Kitatsuji and Rohrer, {Douglas C.} and Khalil Ahmed",

note = "Funding Information: This research was supported by the National Institutes of Health, DHHS (Grant HL 21457), and the Veterans Administration Medical Research Fund. The organization and analysis of the data base associated with this investigation were carried out in part with the use of the PROPHET system, a unique national resource sponsored by the NIH. Information about PROPHET, including how to apply for access, can be obtained from the Director, Chemical/Biological Information-Handling Program, Division of Research Resources, NIH, Bethesda, MD 20205. The technical assistance of the late Mr Fred Andrews and Mr Michael Barone and skillful manuscript preparation by Ms Mary Bougetz are gratefully acknowledged.",

year = "1984",

month = sep,

doi = "10.1016/S0022-2828(84)80007-3",

language = "English (US)",

volume = "16",

pages = "835--842",

journal = "Journal of Molecular and Cellular Cardiology",

issn = "0022-2828",

publisher = "Academic Press Inc.",

number = "9",

}

TY - JOUR

T1 - The inotropic activity of digitalis genins is dependent upon C(17) side-group carbonyl oxygen position

AU - From, Arthur H.L.

AU - Fullerton, Dwight S.

AU - Deffo, Tamboue

AU - Kitatsuji, Eitaro

AU - Rohrer, Douglas C.

AU - Ahmed, Khalil

N1 - Funding Information: This research was supported by the National Institutes of Health, DHHS (Grant HL 21457), and the Veterans Administration Medical Research Fund. The organization and analysis of the data base associated with this investigation were carried out in part with the use of the PROPHET system, a unique national resource sponsored by the NIH. Information about PROPHET, including how to apply for access, can be obtained from the Director, Chemical/Biological Information-Handling Program, Division of Research Resources, NIH, Bethesda, MD 20205. The technical assistance of the late Mr Fred Andrews and Mr Michael Barone and skillful manuscript preparation by Ms Mary Bougetz are gratefully acknowledged.

PY - 1984/9

Y1 - 1984/9

N2 - The inotropic potencies of four digitalis genins were studied utilizing cat left atrial strips. The genin concentration required to induce a 50% increase of isometric tension (T50) was found to closely correlate with the degree of displacement (D) of the C(17) side-group carbonyl oxygen from the position of that atom in digitoxigenin. The line of regression was: log T50=0.54D-6.85, r2=0.98, P0.008. These observations were related to recently reported cat ventricular Na+, K+-ATPase inhibitory potencies of the same genins [expressed as 50% inhibitory (I50) concentrations]. I50 correlated strongly with T50: log I50=0.78 log T50-1.68, r2=0.99, P0.003. Thus, the activity of digitalis genins towards their receptor in intact cardiac tissue is closely related to genin carbonyl oxygen position as well as to Na+, K+-ATPase inhibitory activity. These results further support our earlier conclusions, based upon isolated Na+, K+-ATPase studies, that the digitalis genin C(17) side-group carbonyl oxygen position versus activity relationship is biologically relevant and may prove to be a useful unifying structural model in the further elucidation of the mechanism of digitalis-receptor interactions.

AB - The inotropic potencies of four digitalis genins were studied utilizing cat left atrial strips. The genin concentration required to induce a 50% increase of isometric tension (T50) was found to closely correlate with the degree of displacement (D) of the C(17) side-group carbonyl oxygen from the position of that atom in digitoxigenin. The line of regression was: log T50=0.54D-6.85, r2=0.98, P0.008. These observations were related to recently reported cat ventricular Na+, K+-ATPase inhibitory potencies of the same genins [expressed as 50% inhibitory (I50) concentrations]. I50 correlated strongly with T50: log I50=0.78 log T50-1.68, r2=0.99, P0.003. Thus, the activity of digitalis genins towards their receptor in intact cardiac tissue is closely related to genin carbonyl oxygen position as well as to Na+, K+-ATPase inhibitory activity. These results further support our earlier conclusions, based upon isolated Na+, K+-ATPase studies, that the digitalis genin C(17) side-group carbonyl oxygen position versus activity relationship is biologically relevant and may prove to be a useful unifying structural model in the further elucidation of the mechanism of digitalis-receptor interactions.

KW - C(17) side-group carbonyl oxygen position

KW - Digitalis genins

KW - Inotropism

UR - http://www.scopus.com/inward/record.url?scp=0021613763&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021613763&partnerID=8YFLogxK

U2 - 10.1016/S0022-2828(84)80007-3

DO - 10.1016/S0022-2828(84)80007-3

M3 - Article

C2 - 6092652

AN - SCOPUS:0021613763

SN - 0022-2828

VL - 16

SP - 835

EP - 842

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

IS - 9

ER -

The inotropic activity of digitalis genins is dependent upon C(17) side-group carbonyl oxygen position

Abstract

Bibliographical note

Keywords

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this