Effects of pimobendan and its active metabolite, UD-CG 212 Cl, on Ca2+-activated K+ channels in vascular smooth-muscle cells

Journal of Cardiovascular Pharmacology
C H ChenM Kubo

Abstract

The aim of this study was to clarify the mechanisms of activation of Ca2+-dependent K+ (K(Ca)) channels by pimobendan, a new cardiotonic and vasodilator agent with phosphodiesterase inhibition properties, and its main metabolite, UD-CG 212 Cl, in vascular smooth-muscle cells from porcine coronary arteries. Both pimobendan and UD-CG 212 Cl induced relaxation of porcine coronary artery strips. However, in the presence of 100 microM Rp-cAMPS (Rp diastereomer of adenosine cyclic 3',5'-phosphorothioate), a membrane-permeable antagonist of cAMP, the effects of pimobendan decreased significantly. Application of 1 microM pimobendan activated K(Ca) channels in cell-attached patches, and this increase in activity was suppressed by 100 nM H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide), a cAMP-dependent protein-kinase inhibitor. Pimobendan was ineffective in altering the activity of K(Ca) channels in inside-out patches. In contrast, UD-CG 212 Cl, at a concentration of 1 microM, activated K(Ca) channels not only in cell-attached patches but also in inside-out patches. Application of 100 nM H-89 also inhibited UD-CG 212 Cl-induced K(Ca) channels activity but to a lesser degree than that induced by pimobendan in cell-atta...Continue Reading

References

Aug 1, 1988·Journal of Clinical Pharmacology·A Ohnishi, T Ishizaki
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Jan 4, 1994·European Journal of Pharmacology·S P OlesenJ Drejer
Jan 15, 1993·Biochemical and Biophysical Research Communications·K MinamiY Nakaya

❮ Previous
Next ❯

Citations

Feb 3, 2006·Cardiovascular Drugs and Therapy·Klara BrixiusRobert H G Schwinger
Aug 30, 2012·Journal of Veterinary Emergency and Critical Care·Kimberly L Boyle, Elizabeth Leech

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.