Effects of MCI-154 on Ca2+ activation of skinned human myocardium

Cynthia L. Perreault; Frank V. Brozovich; Bernard J. Ransil; James P. Morgan

doi:10.1016/0014-2999(89)90726-7

Effects of MCI-154 on Ca²⁺ activation of skinned human myocardium

Cynthia L. Perreault
, Frank V. Brozovich
, Bernard J. Ransil
, James P. Morgan

Cardiovascular Medicine

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

30 Scopus citations

Abstract

We investigated the effects of MCI-154, a new inotropic agent, on tension development in saponin-skinned human trabeculae carneae. The skinned fibers were activated by buffer solutions containing varying concentrations of Ca²⁺ (10^-8-10^-4 M). In the sigmoidal tension vs. pCa (-log[Ca²⁺]M) relationship, the Ca²⁺ concentration required for half-maximal activation was shifted leftward in the presence of MCI-154. Furthermore, maximal Ca²⁺-activated tension development was increased in a concentration-dependent manner by MCI-154. Our results suggest that the inotropic effect of MCI-154 may be due, in part, to an increased sensitivity of the myofilaments to Ca²⁺ and enhancement of maximal Ca²⁺-activated tension development.

Original language	English (US)
Pages (from-to)	305-308
Number of pages	4
Journal	European Journal of Pharmacology
Volume	165
Issue number	2-3
DOIs	https://doi.org/10.1016/0014-2999(89)90726-7
State	Published - Jun 20 1989

Keywords

Imidazole
Inotropic drugs
MCI-154
Myocardium (human)
Pyridazinone
Skinned fibers

ASJC Scopus subject areas

Pharmacology

Access to Document

10.1016/0014-2999(89)90726-7

Cite this

@article{357ade6ddc644785bdaa4719632729d6,

title = "Effects of MCI-154 on Ca2+ activation of skinned human myocardium",

abstract = "We investigated the effects of MCI-154, a new inotropic agent, on tension development in saponin-skinned human trabeculae carneae. The skinned fibers were activated by buffer solutions containing varying concentrations of Ca2+ (10-8-10-4 M). In the sigmoidal tension vs. pCa (-log[Ca2+]M) relationship, the Ca2+ concentration required for half-maximal activation was shifted leftward in the presence of MCI-154. Furthermore, maximal Ca2+-activated tension development was increased in a concentration-dependent manner by MCI-154. Our results suggest that the inotropic effect of MCI-154 may be due, in part, to an increased sensitivity of the myofilaments to Ca2+ and enhancement of maximal Ca2+-activated tension development.",

keywords = "Imidazole, Inotropic drugs, MCI-154, Myocardium (human), Pyridazinone, Skinned fibers",

author = "Perreault, \{Cynthia L.\} and Brozovich, \{Frank V.\} and Ransil, \{Bernard J.\} and Morgan, \{James P.\}",

note = "Funding Information: This work was supported in part by U.S. Public Health Service Grants HL31117, DA05171, and a Research Career Funding Information: Development Award (HL01611) to J.P.M. Fellowship support to F.V.B. is provided by the Clinician Investigator Program of the Department of Medicine, Beth Israel Hospital. Data organization and analysis were performed on the Prophet system, a national computer resource sponsored by the Division of Research Resources, National Institutes of Health. The authors would like to thank Mitsubishi Kasei Corporation of Japan for their generous supply of MCI-154 and Robin Rubendunst for typing the manuscript.",

year = "1989",

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AU - Ransil, Bernard J.

AU - Morgan, James P.

N1 - Funding Information: This work was supported in part by U.S. Public Health Service Grants HL31117, DA05171, and a Research Career Funding Information: Development Award (HL01611) to J.P.M. Fellowship support to F.V.B. is provided by the Clinician Investigator Program of the Department of Medicine, Beth Israel Hospital. Data organization and analysis were performed on the Prophet system, a national computer resource sponsored by the Division of Research Resources, National Institutes of Health. The authors would like to thank Mitsubishi Kasei Corporation of Japan for their generous supply of MCI-154 and Robin Rubendunst for typing the manuscript.

PY - 1989/6/20

Y1 - 1989/6/20

N2 - We investigated the effects of MCI-154, a new inotropic agent, on tension development in saponin-skinned human trabeculae carneae. The skinned fibers were activated by buffer solutions containing varying concentrations of Ca2+ (10-8-10-4 M). In the sigmoidal tension vs. pCa (-log[Ca2+]M) relationship, the Ca2+ concentration required for half-maximal activation was shifted leftward in the presence of MCI-154. Furthermore, maximal Ca2+-activated tension development was increased in a concentration-dependent manner by MCI-154. Our results suggest that the inotropic effect of MCI-154 may be due, in part, to an increased sensitivity of the myofilaments to Ca2+ and enhancement of maximal Ca2+-activated tension development.

AB - We investigated the effects of MCI-154, a new inotropic agent, on tension development in saponin-skinned human trabeculae carneae. The skinned fibers were activated by buffer solutions containing varying concentrations of Ca2+ (10-8-10-4 M). In the sigmoidal tension vs. pCa (-log[Ca2+]M) relationship, the Ca2+ concentration required for half-maximal activation was shifted leftward in the presence of MCI-154. Furthermore, maximal Ca2+-activated tension development was increased in a concentration-dependent manner by MCI-154. Our results suggest that the inotropic effect of MCI-154 may be due, in part, to an increased sensitivity of the myofilaments to Ca2+ and enhancement of maximal Ca2+-activated tension development.

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KW - Inotropic drugs

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KW - Pyridazinone

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