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.
|Number of pages||10|
|Journal||Journal of Molecular and Cellular Cardiology|
|State||Published - Jun 1985|
Bibliographical noteFunding 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).
- Adenylate cyclase
- Beta receptors
- Cyclic AMP
- Spare receptors
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine