title: The effect of adenosine deaminase inhibition on the A1 adenosinergic and M2 muscarinergic control of contractility in eu- and hyperthyroid guinea pig atria.
abstract: The A1 adenosine and M2 muscarinic receptors exert protective (including energy consumption limiting) effects in the heart. We investigated the influence of adenosine deaminase (ADA) inhibition on a representative energy consumption limiting function, the direct negative inotropic effect elicited by the A1 adenosinergic and M2 muscarinergic systems, in eu- and hyperthyroid atria. Furthermore, we compared the change in the interstitial adenosine level caused by ADA inhibition and nucleoside transport blockade, two well-established processes to stimulate the cell surface A1 adenosine receptors, in both thyroid states. A classical isolated organ technique was applied supplemented with the receptorial responsiveness method (RRM), a concentration estimating procedure. Via measuring the contractile force, the direct negative inotropic capacity of N(6)-cyclopentyladenosine, a selective A1 receptor agonist, and methacholine, a muscarinic receptor agonist, was determined on the left atria isolated from 8-day solvent- and thyroxine-treated guinea pigs in the presence and absence of 2'-deoxycoformycin, a selective ADA inhibitor, and NBTI, a selective nucleoside transporter inhibitor. We found that ADA inhibition (but not nucleoside transport blockade) increased the signal amplification of the A1 adenosinergic (but not M2 muscarinergic) system. This action of ADA inhibition developed in both thyroid states, but it was greater in hyperthyroidism. Nevertheless, ADA inhibition produced a smaller rise in the interstitial adenosine concentration than nucleoside transport blockade did in both thyroid states. Our results indicate that ADA inhibition, besides increasing the interstitial adenosine level, intensifies the atrial A1 adenosinergic function in another (thyroid hormone-sensitive) way, suggesting a new mechanism of action of ADA inhibition.
authors: Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary.
authors: Krisztian
authors: K
authors: Pak
authors: Judit
authors: J
authors: Zsuga
authors: Zita
authors: Z
authors: Kepes
authors: Tamas
authors: T
authors: Erdei
authors: Balazs
authors: B
authors: Varga
authors: Bela
authors: B
authors: Juhasz
authors: Andras Jozsef
authors: AJ
authors: Szentmiklosi
authors: Rudolf
authors: R
authors: Gesztelyi
mesh_terms: D000241:Adenosine / Q000502:physiology; D000243:Adenosine Deaminase / Q000502:physiology*; D058892:Adenosine Deaminase Inhibitors / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology*; D006980:Hyperthyroidism / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D015649:Pentostatin / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D043585:Receptor, Muscarinic M2 / Q000502:physiology*; D013974:Thyroxine / Q000494:pharmacology
chemical_list: D058892:Adenosine Deaminase Inhibitors; D043682:Receptor, Adenosine A1; D043585:Receptor, Muscarinic M2; D015649:Pentostatin; D000243:Adenosine Deaminase; D000241:Adenosine; D013974:Thyroxine