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The effect of adenosine deaminase inhibition on the A1 adenosinergic and M2 muscarinergic control of contractility in eu- and hyperthyroid guinea pig atria.

Pak K, Zsuga J, Kepes Z, Erdei T, Varga B, Juhasz B, Szentmiklosi AJ, Gesztelyi R - Naunyn Schmiedebergs Arch. Pharmacol. (2015)

Bottom Line: The A1 adenosine and M2 muscarinic receptors exert protective (including energy consumption limiting) effects in the heart.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary.

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.

No MeSH data available.


Related in: MedlinePlus

The contractile force of guinea pig left atria in the different groups before and after the in vitro treatment. The open columns show the contractile forces of atria measured before the in vitro treatment (mean + SEM). The shorter filled columns in front of the open ones denote the contractile forces determined at the end of the in vitro treatment (mean − SEM). The homogeneous light grey filling means an in vitro treatment containing neither NBTI nor DCF, while light grey filling with darker or less dark pattern shows an in vitro treatment containing NBTI or DCF, respectively. Group names are indicated below the columns. Comparing the contractile forces of the different in vitro-treated groups (filled columns), a significant difference was found only in the case of NBTI: S Co vs. S NBTI, S CPX vs. S NBTI, T Co vs. T NBTI, and T CPX vs. T NBTI (asterisk)
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Fig2: The contractile force of guinea pig left atria in the different groups before and after the in vitro treatment. The open columns show the contractile forces of atria measured before the in vitro treatment (mean + SEM). The shorter filled columns in front of the open ones denote the contractile forces determined at the end of the in vitro treatment (mean − SEM). The homogeneous light grey filling means an in vitro treatment containing neither NBTI nor DCF, while light grey filling with darker or less dark pattern shows an in vitro treatment containing NBTI or DCF, respectively. Group names are indicated below the columns. Comparing the contractile forces of the different in vitro-treated groups (filled columns), a significant difference was found only in the case of NBTI: S Co vs. S NBTI, S CPX vs. S NBTI, T Co vs. T NBTI, and T CPX vs. T NBTI (asterisk)

Mentions: The initial contractile forces, measured prior to the in vitro treatment (before the first E/c curve), did not differ significantly either between the pooled solvent- and T4-treated atria (9.3 ± 0.35 and 8.67 ± 0.4 mN, respectively) or among the different groups (Fig. 2).Fig. 2


The effect of adenosine deaminase inhibition on the A1 adenosinergic and M2 muscarinergic control of contractility in eu- and hyperthyroid guinea pig atria.

Pak K, Zsuga J, Kepes Z, Erdei T, Varga B, Juhasz B, Szentmiklosi AJ, Gesztelyi R - Naunyn Schmiedebergs Arch. Pharmacol. (2015)

The contractile force of guinea pig left atria in the different groups before and after the in vitro treatment. The open columns show the contractile forces of atria measured before the in vitro treatment (mean + SEM). The shorter filled columns in front of the open ones denote the contractile forces determined at the end of the in vitro treatment (mean − SEM). The homogeneous light grey filling means an in vitro treatment containing neither NBTI nor DCF, while light grey filling with darker or less dark pattern shows an in vitro treatment containing NBTI or DCF, respectively. Group names are indicated below the columns. Comparing the contractile forces of the different in vitro-treated groups (filled columns), a significant difference was found only in the case of NBTI: S Co vs. S NBTI, S CPX vs. S NBTI, T Co vs. T NBTI, and T CPX vs. T NBTI (asterisk)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4495724&req=5

Fig2: The contractile force of guinea pig left atria in the different groups before and after the in vitro treatment. The open columns show the contractile forces of atria measured before the in vitro treatment (mean + SEM). The shorter filled columns in front of the open ones denote the contractile forces determined at the end of the in vitro treatment (mean − SEM). The homogeneous light grey filling means an in vitro treatment containing neither NBTI nor DCF, while light grey filling with darker or less dark pattern shows an in vitro treatment containing NBTI or DCF, respectively. Group names are indicated below the columns. Comparing the contractile forces of the different in vitro-treated groups (filled columns), a significant difference was found only in the case of NBTI: S Co vs. S NBTI, S CPX vs. S NBTI, T Co vs. T NBTI, and T CPX vs. T NBTI (asterisk)
Mentions: The initial contractile forces, measured prior to the in vitro treatment (before the first E/c curve), did not differ significantly either between the pooled solvent- and T4-treated atria (9.3 ± 0.35 and 8.67 ± 0.4 mN, respectively) or among the different groups (Fig. 2).Fig. 2

Bottom Line: The A1 adenosine and M2 muscarinic receptors exert protective (including energy consumption limiting) effects in the heart.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary.

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.

No MeSH data available.


Related in: MedlinePlus