The effects of trimetoquinol on the intact rabbit heart and myocardial adenylate cyclase activity: Evidence for spare myocardial beta receptors

Michael Babich; John Atkinson; Michael T. Piascik

doi:10.1016/S0022-2828(85)80025-0

The effects of trimetoquinol on the intact rabbit heart and myocardial adenylate cyclase activity: Evidence for spare myocardial beta receptors

Michael Babich, John Atkinson, Michael T. Piascik

Pharmacology and Nutritional Sciences

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

7 Scopus citations

Abstract

We have compared and contrasted the actions of (-)isoproterenol and (±) trimetoquinol on rabbit heart preparations. In the presence of either GTP or Gpp[NH]_p (guanosine-5′-(β, γ imino)triphosphate), trimetoquinol displayed partial agonist activity in stimulating adenylate cyclase activity in a particulate rabbit heart preparation. Trimetoquinol enhanced adenylate cyclase activity 20% or 65% of the maximum obtainable by isoproterenol in the presence of GTP or Gpp[NH]_p respectively. In the presence of GTP, concentrations of catecholamines required to enhance cyclase activity 15% of the maximum obtainable with isoproterenol (EC₁₅) were 2.0×10^-7 m and 5.5×10^-8 m for trimetoquinol and isoproterenol, respectively. In the presence of Gpp[NH]_p EC₃₀ values were 2.0×10^-7 and 3.5×10^-8 m for trimetoquinol and isoproterenol respectively. Trimetoquinol also displayed partial agonist activity for the ability to increase cAMP levels in the isolated perfused rabbit heart. By contrast trimetoquinol was equieffective to isoproterenol at increasing tension development and rate of contraction of the isolated perfused heart. Concentrations of catecholamines required to increase tension and rate of contraction 50% of the maximum obtainable with isoproterenol were 1.5×10^-7 m and 1.7×10^-8 m for trimetoquinol and isoproterenol, respectively. These data show that only a partial stimulation of adenylate cyclase activity and cAMP levels by trimetoquinol is sufficient to produce maximal changes in mechanical activity of the heart. These data support the concept of spare myocardial beta receptors because: (1) trimetoquinol is much less effective than isoproterenol at stimulating adenylate cyclase activity and cAMP levels, yet is equal to isoproterenol at producing changes in mechanical activity of the intact heart and (2) Isoproterenol concentrations which produce maximal increases in rate and developed tension in the intact heart enhance adenylate cyclase activity only 20% of maximum.

Original language	English
Pages (from-to)	565-574
Number of pages	10
Journal	Journal of Molecular and Cellular Cardiology
Volume	17
Issue number	6
DOIs	https://doi.org/10.1016/S0022-2828(85)80025-0
State	Published - Jun 1985

Bibliographical note

Funding Information:
* These data were presented in preliminary form at the American Society for Pharmacology and Experimental Therapeutics meetings in Philadelphia, Pennsylvania 1983. t This work was supported by grants from: The Isabell Kircher Fund; Predoctoral Training Grant (MB and JA); The American Heart Association, Kentucky Affiliate; Pharmaceutical Manufacturers Association Foundation; Lilly Research Laboratories; PSP Fund of the University of Kentucky (MTP).

Keywords

Adenylate cyclase
Beta receptors
Cyclic AMP
Isoproterenol
Spare receptors
Trimetoquinol

ASJC Scopus subject areas

Molecular Biology
Cardiology and Cardiovascular Medicine

Access to Document

10.1016/S0022-2828(85)80025-0

Cite this

@article{ae5859319fa94197b0d125090ea38cd1,

title = "The effects of trimetoquinol on the intact rabbit heart and myocardial adenylate cyclase activity: Evidence for spare myocardial beta receptors",

abstract = "We have compared and contrasted the actions of (-)isoproterenol and (±) trimetoquinol on rabbit heart preparations. In the presence of either GTP or Gpp[NH]p (guanosine-5′-(β, γ imino)triphosphate), trimetoquinol displayed partial agonist activity in stimulating adenylate cyclase activity in a particulate rabbit heart preparation. Trimetoquinol enhanced adenylate cyclase activity 20% or 65% of the maximum obtainable by isoproterenol in the presence of GTP or Gpp[NH]p respectively. In the presence of GTP, concentrations of catecholamines required to enhance cyclase activity 15% of the maximum obtainable with isoproterenol (EC15) were 2.0×10-7 m and 5.5×10-8 m for trimetoquinol and isoproterenol, respectively. In the presence of Gpp[NH]p EC30 values were 2.0×10-7 and 3.5×10-8 m for trimetoquinol and isoproterenol respectively. Trimetoquinol also displayed partial agonist activity for the ability to increase cAMP levels in the isolated perfused rabbit heart. By contrast trimetoquinol was equieffective to isoproterenol at increasing tension development and rate of contraction of the isolated perfused heart. Concentrations of catecholamines required to increase tension and rate of contraction 50% of the maximum obtainable with isoproterenol were 1.5×10-7 m and 1.7×10-8 m for trimetoquinol and isoproterenol, respectively. These data show that only a partial stimulation of adenylate cyclase activity and cAMP levels by trimetoquinol is sufficient to produce maximal changes in mechanical activity of the heart. These data support the concept of spare myocardial beta receptors because: (1) trimetoquinol is much less effective than isoproterenol at stimulating adenylate cyclase activity and cAMP levels, yet is equal to isoproterenol at producing changes in mechanical activity of the intact heart and (2) Isoproterenol concentrations which produce maximal increases in rate and developed tension in the intact heart enhance adenylate cyclase activity only 20% of maximum.",

keywords = "Adenylate cyclase, Beta receptors, Cyclic AMP, Isoproterenol, Spare receptors, Trimetoquinol",

author = "Michael Babich and John Atkinson and Piascik, {Michael T.}",

note = "Funding Information: * These data were presented in preliminary form at the American Society for Pharmacology and Experimental Therapeutics meetings in Philadelphia, Pennsylvania 1983. t This work was supported by grants from: The Isabell Kircher Fund; Predoctoral Training Grant (MB and JA); The American Heart Association, Kentucky Affiliate; Pharmaceutical Manufacturers Association Foundation; Lilly Research Laboratories; PSP Fund of the University of Kentucky (MTP).",

year = "1985",

month = jun,

doi = "10.1016/S0022-2828(85)80025-0",

language = "English",

volume = "17",

pages = "565--574",

number = "6",

}

TY - JOUR

T1 - The effects of trimetoquinol on the intact rabbit heart and myocardial adenylate cyclase activity

T2 - Evidence for spare myocardial beta receptors

AU - Babich, Michael

AU - Atkinson, John

AU - Piascik, Michael T.

N1 - Funding Information: * These data were presented in preliminary form at the American Society for Pharmacology and Experimental Therapeutics meetings in Philadelphia, Pennsylvania 1983. t This work was supported by grants from: The Isabell Kircher Fund; Predoctoral Training Grant (MB and JA); The American Heart Association, Kentucky Affiliate; Pharmaceutical Manufacturers Association Foundation; Lilly Research Laboratories; PSP Fund of the University of Kentucky (MTP).

PY - 1985/6

Y1 - 1985/6

N2 - We have compared and contrasted the actions of (-)isoproterenol and (±) trimetoquinol on rabbit heart preparations. In the presence of either GTP or Gpp[NH]p (guanosine-5′-(β, γ imino)triphosphate), trimetoquinol displayed partial agonist activity in stimulating adenylate cyclase activity in a particulate rabbit heart preparation. Trimetoquinol enhanced adenylate cyclase activity 20% or 65% of the maximum obtainable by isoproterenol in the presence of GTP or Gpp[NH]p respectively. In the presence of GTP, concentrations of catecholamines required to enhance cyclase activity 15% of the maximum obtainable with isoproterenol (EC15) were 2.0×10-7 m and 5.5×10-8 m for trimetoquinol and isoproterenol, respectively. In the presence of Gpp[NH]p EC30 values were 2.0×10-7 and 3.5×10-8 m for trimetoquinol and isoproterenol respectively. Trimetoquinol also displayed partial agonist activity for the ability to increase cAMP levels in the isolated perfused rabbit heart. By contrast trimetoquinol was equieffective to isoproterenol at increasing tension development and rate of contraction of the isolated perfused heart. Concentrations of catecholamines required to increase tension and rate of contraction 50% of the maximum obtainable with isoproterenol were 1.5×10-7 m and 1.7×10-8 m for trimetoquinol and isoproterenol, respectively. These data show that only a partial stimulation of adenylate cyclase activity and cAMP levels by trimetoquinol is sufficient to produce maximal changes in mechanical activity of the heart. These data support the concept of spare myocardial beta receptors because: (1) trimetoquinol is much less effective than isoproterenol at stimulating adenylate cyclase activity and cAMP levels, yet is equal to isoproterenol at producing changes in mechanical activity of the intact heart and (2) Isoproterenol concentrations which produce maximal increases in rate and developed tension in the intact heart enhance adenylate cyclase activity only 20% of maximum.

AB - We have compared and contrasted the actions of (-)isoproterenol and (±) trimetoquinol on rabbit heart preparations. In the presence of either GTP or Gpp[NH]p (guanosine-5′-(β, γ imino)triphosphate), trimetoquinol displayed partial agonist activity in stimulating adenylate cyclase activity in a particulate rabbit heart preparation. Trimetoquinol enhanced adenylate cyclase activity 20% or 65% of the maximum obtainable by isoproterenol in the presence of GTP or Gpp[NH]p respectively. In the presence of GTP, concentrations of catecholamines required to enhance cyclase activity 15% of the maximum obtainable with isoproterenol (EC15) were 2.0×10-7 m and 5.5×10-8 m for trimetoquinol and isoproterenol, respectively. In the presence of Gpp[NH]p EC30 values were 2.0×10-7 and 3.5×10-8 m for trimetoquinol and isoproterenol respectively. Trimetoquinol also displayed partial agonist activity for the ability to increase cAMP levels in the isolated perfused rabbit heart. By contrast trimetoquinol was equieffective to isoproterenol at increasing tension development and rate of contraction of the isolated perfused heart. Concentrations of catecholamines required to increase tension and rate of contraction 50% of the maximum obtainable with isoproterenol were 1.5×10-7 m and 1.7×10-8 m for trimetoquinol and isoproterenol, respectively. These data show that only a partial stimulation of adenylate cyclase activity and cAMP levels by trimetoquinol is sufficient to produce maximal changes in mechanical activity of the heart. These data support the concept of spare myocardial beta receptors because: (1) trimetoquinol is much less effective than isoproterenol at stimulating adenylate cyclase activity and cAMP levels, yet is equal to isoproterenol at producing changes in mechanical activity of the intact heart and (2) Isoproterenol concentrations which produce maximal increases in rate and developed tension in the intact heart enhance adenylate cyclase activity only 20% of maximum.

KW - Adenylate cyclase

KW - Beta receptors

KW - Cyclic AMP

KW - Isoproterenol

KW - Spare receptors

KW - Trimetoquinol

UR - http://www.scopus.com/inward/record.url?scp=0021880685&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021880685&partnerID=8YFLogxK

U2 - 10.1016/S0022-2828(85)80025-0

DO - 10.1016/S0022-2828(85)80025-0

M3 - Article

C2 - 2991540

AN - SCOPUS:0021880685

SN - 0022-2828

VL - 17

SP - 565

EP - 574

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

IS - 6

ER -

The effects of trimetoquinol on the intact rabbit heart and myocardial adenylate cyclase activity: Evidence for spare myocardial beta receptors

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this