Antagonism of novel inotropic agents at A1 adenosine receptors and m-cholinoceptors in human myocardium.

Abstract

The effects of the new inotropic agents saterinone, sulmazole, UD-CG 212.Cl and milrinone at A1 adenosine receptors and m-cholinoceptors were evaluated in human myocardium from patients with heart failure. At A1 adenosine receptors, all compounds inhibited 3H-DPCPX-binding to ventricular membrane preparations at micromolar concentrations. As judged from the K1-values, the rank order of potency was saterinone greater than sulmazole greater than UD-CG 212.Cl greater than milrinone. The new inotropic agents also displaced the binding of 3H-QNB at m-cholinoceptors. Except for saterinone, the concentration ranges of mean Ki-values were considerably higher at m-cholinoceptors than at A1 adenosine receptors. The rank order of potency was saterinone greater than sulmazole greater than UD-CG 212.Cl greater than milrinone. Competition of the A1 adenosine receptor agonist R-PIA to 3H-DPCPX-binding showed a biphasic curve with a shallow slope (Hill coefficient nH = 0.63) and revealed two affinity states of the A1 adenosine receptor. In the presence of guanine nucleotides [Gpp(NH)p], the competition curve showed one low affinity class of binding sites and was shifted to the right. In contrast, the competition curves of the new inotropic agents were characterized by a monophasic, steeper slope (mean Hill coefficient nH = 0.98). Guanine nucleotides had no effect. Similar results were obtained with saterinone and carbachol at m-cholinoceptors. Competition with carbachol revealed three affinity states of the m-cholinoceptor, the super-high affinity binding was reversed by Gpp(NH)p. Competition with saterinone revealed one class of binding sites which was not influenced by Gpp(NH)p.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: M Ungerer, M Böhm, R H Schwinger, E Erdmann
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 341 Issue 6 Pg. 577-85 (Jun 1990) ISSN: 0028-1298 [Print] Germany
• PMID: 2392160 (Publication Type: Journal Article)

Chemical References

• Cardiotonic Agents
• Imidazoles
• Piperazines
• Pyridazines
• Pyridones
• Receptors, Cholinergic
• Receptors, Purinergic
• Xanthines
• Guanylyl Imidodiphosphate
• Quinuclidinyl Benzilate
• UD CG 212 Cl
• 1,3-dipropyl-8-cyclopentylxanthine
• sulmazole
• Milrinone
• saterinone

Topics

• Adult
• Binding, Competitive (drug effects)
• Cardiotonic Agents (antagonists & inhibitors)
• Electric Stimulation
• Guanylyl Imidodiphosphate (pharmacology)
• Heart (drug effects)
• Heart Failure (metabolism)
• Humans
• Imidazoles (pharmacology)
• In Vitro Techniques
• Membranes (drug effects, metabolism)
• Milrinone
• Myocardium (metabolism)
• Piperazines (pharmacology)
• Pyridazines (pharmacology)
• Pyridones (pharmacology)
• Quinuclidinyl Benzilate
• Receptors, Cholinergic (drug effects)
• Receptors, Purinergic (drug effects)
• Xanthines