Conant, A.R. and Jarvis, S.M. (1994) Nucleoside Influx and Efflux in Guinea-Pig Ventricular Myocytes - Inhibition by Analogs of Lidoflazine. Biochemical Pharmacology, 48 (5). pp. 873-880. ISSN 0006-2952.
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Adenosine influx and formycin B influx and efflux were characterized in guinea-pig ventricular myocytes at 22 degrees. Transport by both modes was saturable and inhibited by nitrobenzylthioinosine (NBMPR), indicating the presence of an equilibrative NBMPR-sensitive nucleoside transporter in the cardiomyocytes. The kinetic constants for influx and efflux of formycin B, a non-metabolized nucleoside, were similar, suggesting that the nucleoside transporter exhibits symmetrical kinetics (apparent K-m 490 +/- 160 and 700 +/- 140 mu M; V-max, 6.5 +/- 1.7 and 3.5 +/- 0.3 nmol/10(6) cells per min for influx and efflux, respectively). No evidence was found of either NBMPR-insensitive equilibrative nucleoside transport or sodium-dependent concentrative nucleoside transport. Inhibition of adenosine influx (apparent K(m)100 +/- 33 mu M), by lidoflazine and the analogues mioflazine, soluflazine and R73-335, gave average K-i values of 730, 100, 64 and 2.9 nM, respectively. These compounds also inhibited formycin B efflux with a similar potency to that of adenosine influx. NBMPR-sensitive nucleoside transport was associated with high affinity binding of NBMPR (apparent K-d similar to 1 nM; 9.6 x 10(5) sites/cell). Specific binding of NBMPR was also inhibited by lidoflazine and its analogues. Mioflazine and soluflazine were 20-30-fold more potent at inhibiting NBMPR-sensitive nucleoside influx in guinea-pig erythrocytes than ventricular myocytes, indicating that the potency of some of the compounds studied is tissue dependent.
|Uncontrolled keywords:||ADENOSINE TRANSPORT; NITROBENZYTHIOINOSINE; FORMYCIN B; CARDIOMYOCYTES; NA+/NUCLEOSIDE TRANSPORTER (SNST1)|
|Subjects:||R Medicine > RM Therapeutics. Pharmacology|
|Divisions:||Faculties > Science Technology and Medical Studies > Medway School of Pharmacy|
|Depositing User:||P. Ogbuji|
|Date Deposited:||02 Jul 2009 15:40|
|Last Modified:||17 Jul 2012 11:01|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/20466 (The current URI for this page, for reference purposes)|
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