Influence of hyperthyroidism on the effect of adenosine transport blockade assessed by a novel method in guinea pig atria.
The aim of the present study was to investigate the effect of hyperthyroidism on the trans-sarcolemmal adenosine (Ado) flux via equilibrative and nitrobenzylthioinosine (NBTI)-sensitive nucleoside transporters (ENT1) in guinea pig atria, by assessing the change in the Ado concentration of the interstitial fluid ([Ado]ISF) under nucleoside transport blockade with NBTI. For the assessment, we applied our novel method, which estimates the change in [Ado]ISF utilizing the altered inotropic response to N6-cyclopentyladenosine (CPA), a relative stable selective agonist of A1 Ado receptors, by providing a relative index, the equivalent concentration of CPA. Our results show an interstitial Ado accumulation upon ENT1 blockade, which was more extensive in the hyperthyroid samples (CPA concentrations equieffective with the surplus [Ado]ISF were two to three times higher in hyperthyroid atria than in euthyroid ones, with regard to the negative inotropic effect of CPA and Ado). This suggests an enhanced Ado influx via ENT1 in hyperthyroid atria. It is concluded that hyperthyroidism does not alter the prevailing direction of the Ado transport, moreover intensifies the Ado influx in the guinea pig atrium.
Karsai
Denes
D
Department of Pharmacology , University of Debrecen, H-4012 Debrecen, PO Box 8, Hungary.
Gesztelyi
Rudolf
R
Zsuga
Judit
J
Jakab
Anita
A
Szendrei
Levente
L
Juhasz
Bela
B
Bak
Istvan
I
Szabo
Gergo
G
Lekli
Istvan
I
Vecsernyes
Miklos
M
Varga
Edit
E
Szentmiklosi
Andras Jozsef
AJ
Tosaki
Arpad
A
D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D003517:Cyclopentanes / Q000737:chemistry; D006168:Guinea Pigs; D006325:Heart Atria / Q000378:metabolism*; D006980:Hyperthyroidism / Q000473:pathology*; D008297:Male; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013961:Thyroid Gland / Q000378:metabolism; D013974:Thyroxine / Q000737:chemistry
D003517:Cyclopentanes; D018047:Receptors, Purinergic P1; D012997:Solvents; D013868:Thioinosine; D000243:Adenosine Deaminase; C001789:4-nitrobenzylthioinosine; D000241:Adenosine; D013974:Thyroxine