title: Influence of hyperthyroidism on the effect of adenosine transport blockade assessed by a novel method in guinea pig atria.
abstract: 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.
authors.affiliation: Department of Pharmacology , University of Debrecen, H-4012 Debrecen, PO Box 8, Hungary.
authors.forename: Denes
authors.initials: D
authors.lastname: Karsai
authors.forename: Rudolf
authors.initials: R
authors.lastname: Gesztelyi
authors.forename: Judit
authors.initials: J
authors.lastname: Zsuga
authors.forename: Anita
authors.initials: A
authors.lastname: Jakab
authors.forename: Levente
authors.initials: L
authors.lastname: Szendrei
authors.forename: Bela
authors.initials: B
authors.lastname: Juhasz
authors.forename: Istvan
authors.initials: I
authors.lastname: Bak
authors.forename: Gergo
authors.initials: G
authors.lastname: Szabo
authors.forename: Istvan
authors.initials: I
authors.lastname: Lekli
authors.forename: Miklos
authors.initials: M
authors.lastname: Vecsernyes
authors.forename: Edit
authors.initials: E
authors.lastname: Varga
authors.forename: Andras Jozsef
authors.initials: AJ
authors.lastname: Szentmiklosi
authors.forename: Arpad
authors.initials: A
authors.lastname: Tosaki
mesh_terms: 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
chemical_list: D003517:Cyclopentanes; D018047:Receptors, Purinergic P1; D012997:Solvents; D013868:Thioinosine; D000243:Adenosine Deaminase; C001789:4-nitrobenzylthioinosine; D000241:Adenosine; D013974:Thyroxine