PT  - JOURNAL ARTICLE
AU  - E E Bagwell
AU  - J G Webb
AU  - T Walle
AU  - T E Gaffney
TI  - Stereoselective uptake of atenolol into storage granules isolated from PC12 cells.
DP  - 1989 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 476--482
VI  - 249
IP  - 2
4099  - http://jpet.aspetjournals.org/content/249/2/476.short
4100  - http://jpet.aspetjournals.org/content/249/2/476.full
SO  - J Pharmacol Exp Ther1989 May 01; 249
AB  - Atenolol has been shown to be stored and secreted from PC12 cells by calcium-dependent and stereoselective mechanisms. The present study was designed to determine if the cytoplasmic amine storage granule was the site for storage and release of atenolol and if the drug was, in fact, an enantiomeric selective substrate for the vesicular amine transport protein. Uptake of racemic [3H]atenolol and (-)-[3H]norepinephrine was studied in a vesicular preparation of storage granules isolated from PC12 cells. Uptake of both molecules was found to be ATP-dependent (80%) and to reach steady state in approximately 10 to 15 min. Uptake and storage was inhibited (95%) by either reserpine, an inhibitor of the vesicular amine carrier, or by nigericin which dissipates the proton gradient across the membrane. Uptake of neither compound was inhibited by desipramine, an inhibitor of uptake 1, or oligomycin, an inhibitor of mitochondrial adenosine triphosphatase. Furthermore, uptake of the (-)-enantiomer of atenolol was found to be approximately 5-fold greater than the (+)-enantiomer. Kinetic studies revealed a Km of 184 microM for (+/-)-atenolol and 79 microM for (-)-norepinephrine and Vmax values of 750 and 503 pmol/min/mg of protein for atenolol and norepinephrine, respectively. The interaction of the two compounds with the transport process was found to be kinetically competitive. In separate experiments, atenolol was also found to be transported stereoselectively into bovine adrenal chromaffin granule ghosts and to be ATP dependent (85%) and reserpine sensitive (44%).(ABSTRACT TRUNCATED AT 250 WORDS)