BIOMAT Database Logo BIOMAT Database Logo

Negative chronotropic and inotropic effects exerted by diadenosine hexaphosphate (AP6A) via A1-adenosine receptors. 1996

U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
Institut für Pharmakologie und Toxikologie, Universität Münster, Germany.

1. Diadenosine hexaphosphate (AP6A) exerts vasoconstrictive effects. The purpose of this study was to investigate whether AP6A has any effect on cardiac function. 2. The effects of AP6A (0.1-100 microM) on cardiac contractility and frequency were studied in guinea-pig and human isolated cardiac preparations. Furthermore, the effects of AP6A on the amplitude of the L-type calcium current, on the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content and on the phosphorylation of regulatory phosphoproteins, i.e. phospholamban and troponin inhibitor, were investigated in guinea-pig isolated ventricular myocytes. 3. In isolated spontaneously beating right atria of the guinea-pig AP6A exerted a negative chronotropic effect and reduced the rate of contraction maximally by 35% (IC20 = 35 microM). 4. In isolated electrically driven left atria of the guinea-pig AP6A exerted a negative inotropic effect and reduced force of contraction maximally by 23% (IC20 = 70 microM). 5. In isolated electrically driven papillary muscles of the guinea-pig AP6A alone was ineffective, but attenuated isoprenaline-stimulated force of contraction maximally by 23% (IC20 = 60 microM). Furthermore, AP6A attenuated the relaxant effect of isoprenaline. 6. In human isolated electrically driven ventricular preparations AP6A alone was ineffective, but attenuated isoprenaline-stimulated force of contraction by maximally 42% (IC20 = 18 microM). Moreover, AP6A attenuated the relaxant effect of isoprenaline. 7. All these effects of AP6A were abolished by the selective A1-adenosine receptor antagonist 1,3-dipropyl-cyclopentyl-xanthine (DPCPX, 0.3 microM), whereas the M-cholinoceptor antagonist atropine (10 microM) and the P2-purinoceptor antagonist suramin (300 microM) failed to abolish the effects of AP6A. 8. AP6A 100 microM had no effect on the amplitude of the L-type calcium current, but attenuated isoprenaline-stimulated L-type calcium current. The maximum of the current-voltage relationship (I-V curve) was shifted to the left by isoprenaline and additional application of AP6A shifted the I-V curve back to the right to the control value. The phosphorylation state of phospholamban and the troponin inhibitor was unchanged by AP6A alone, but was markedly attenuated by AP6A in the presence of isoprenaline. Cyclic AMP levels remained unchanged by AP6A, even after stimulation with isoprenaline. 9. In summary, AP6A exerts negative chronotropic and inotropic effects in guinea-pig and human cardiac preparations. These effects are mediated via A1-adenosine receptors as all effects were sensitive to the selective A1-adenosine receptor antagonist DPCPX. Furthermore, the effects of AP6A on cyclic AMP levels, protein phosphorylation and the L-type calcium current are in accordance with stimulation of A1-adenosine receptors.

UI MeSH Term Description Entries
D008297 Male Males
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015220 Calcium Channels Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. Ion Channels, Calcium,Receptors, Calcium Channel Blocker,Voltage-Dependent Calcium Channel,Calcium Channel,Calcium Channel Antagonist Receptor,Calcium Channel Antagonist Receptors,Calcium Channel Blocker Receptor,Calcium Channel Blocker Receptors,Ion Channel, Calcium,Receptors, Calcium Channel Antagonist,VDCC,Voltage-Dependent Calcium Channels,Calcium Channel, Voltage-Dependent,Calcium Channels, Voltage-Dependent,Calcium Ion Channel,Calcium Ion Channels,Channel, Voltage-Dependent Calcium,Channels, Voltage-Dependent Calcium,Voltage Dependent Calcium Channel,Voltage Dependent Calcium Channels
D015226 Dinucleoside Phosphates A group of compounds which consist of a nucleotide molecule to which an additional nucleoside is attached through the phosphate molecule(s). The nucleotide can contain any number of phosphates. Bis(5'-Nucleosidyl)Oligophosphates,Bis(5'-Nucleosidyl)Phosphates,Deoxydinucleoside Phosphates,Dinucleoside Diphosphates,Dinucleoside Monophosphates,Dinucleoside Oligophosphates,Dinucleoside Tetraphosphates,Dinucleoside Triphosphates,Bis(5'-Nucleosidyl)Tetraphosphate,Dinucleoside Polyphosphates,Diphosphates, Dinucleoside,Monophosphates, Dinucleoside,Oligophosphates, Dinucleoside,Phosphates, Deoxydinucleoside,Phosphates, Dinucleoside,Polyphosphates, Dinucleoside,Tetraphosphates, Dinucleoside,Triphosphates, Dinucleoside
D018047 Receptors, Purinergic P1 A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra). Adenosine Receptors,P1 Purinoceptors,Purinergic P1 Receptors,Receptors, Adenosine,Adenosine Receptor,P1 Purinoceptor,Receptor, Purinergic P1,P1 Receptor, Purinergic,P1 Receptors, Purinergic,Purinergic P1 Receptor,Purinoceptor, P1,Purinoceptors, P1,Receptor, Adenosine

Related Publications

U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
Acyl-CoA synthetase catalyzes the synthesis of diadenosine hexaphosphate (Ap6A).
March 1999, Biochimie,
U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
Potentiation of the negative chronotropic and inotropic effects of adenosine by dipyridamole.
September 1974, The Tohoku journal of experimental medicine,
U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
Potentiation of the negative chronotropic and inotropic effects of adenosine by 2-phenylaminoadenosine.
January 1983, Clinical and experimental pharmacology & physiology,
U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
Negative inotropic and chronotropic effects of delta-opioid receptor antagonists are mediated via non-opioid receptors.
April 2006, Bulletin of experimental biology and medicine,
U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
Negative inotropic and chronotropic effects of oxytocin.
August 2001, Hypertension (Dallas, Tex. : 1979),
U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
Adenosine promotes histamine H1-mediated negative chronotropic and inotropic effects on human atrial myocardium.
December 1988, The Journal of pharmacology and experimental therapeutics,
U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
[Negative chronotropic and inotropic effects of Panax notoginseng saponins].
September 1988, Zhongguo yao li xue bao = Acta pharmacologica Sinica,
U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
Adenosine A1 receptor stimulation antagonizes the negative inotropic effects of the PKC activator dioctanoylglycerol.
May 1998, Journal of molecular and cellular cardiology,
U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
MECHANISM OF NEGATIVE CHRONOTROPIC AND INOTROPIC EFFECTS OF SOME ANTIFIBRILLATORY AGENTS.
February 1964, The American journal of physiology,
U Vahlensieck, and P Bokník, and J Knapp, and B Linck, and F U Müller, and J Neumann, and S Herzig, and H Schlüter, and W Zidek, and M C Deng, and H H Scheld, and W Schmitz
Negative chronotropic and inotropic effects of lubiprostone on iPS cell-derived cardiomyocytes via activation of CFTR.
April 2020, BMC complementary medicine and therapies,
Copied contents to your clipboard!