Selective transport of adenosine into porcine coronary smooth muscle

L. J. Rubin, Lynelle R Johnson, J. R. Dodam, A. K. Dhalla, L. Magliola, M. H. Laughlin, A. W. Jones

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Adenosine (ADO), an endogenous regulator of coronary vascular tone, enhances vasorelaxation in the presence of nucleoside transport inhibitors such as dipyridamole. We tested the hypothesis that coronary smooth muscle (CSM) contains a high-affinity transporter for ADO. ADO-mediated relaxation of isolated large and small porcine coronary artery rings was enhanced 12-fold and 3.4-fold, respectively, by the transport inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI). Enhanced relaxation was independent of endothelium and was selective for ADO over synthetic analogs. Uptake of [3H]ADO into freshly dissociated CSM cells or endothelium-denuded rings was linear and concentration dependent. Kinetic analysis yielded a maximum uptake (V(max)) of 67 ± 7.0 pmol·mg protein-1·min-1 and a Michaelis constant (K(m)) of 10.5 ± 5.8 μM in isolated cells and a V(max) of 5.1 ± 0.5 pmol·min-1·mg wet wt-1 and a K(m) of 17.6 ± 2.6 μM in intact rings. NBTI inhibited transport into small arteries (IC50 = 42 nM) and cells. Analyses of extracellular space and diffusion kinetics using [3H]sucrose indicate the V(max) and K(m) for ADO transport are sufficient to clear a significant amount of extracellular adenosine. These data indicate CSM possess a high-affinity nucleoside transporter and that the activity of this transporter is sufficient to modulate ADO sensitivity of large and small coronary arteries.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number3 48-3
StatePublished - 2000
Externally publishedYes

Keywords

  • 2-chloroadenosine
  • Dipyridamole
  • Erythro-9-(2-hydroxy-3-nonyl)-ad enine hydrochloride
  • S-(4-nitrobenzyl)-6-thioinosine

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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    Rubin, L. J., Johnson, L. R., Dodam, J. R., Dhalla, A. K., Magliola, L., Laughlin, M. H., & Jones, A. W. (2000). Selective transport of adenosine into porcine coronary smooth muscle. American Journal of Physiology - Heart and Circulatory Physiology, 279(3 48-3).