Inhibitory effect of ergot alkaloids on nucleosides transport in cultured bovine anterior pituitary cells

Abstract

Effect of ergot alkaloids on (3H)-nucleosides uptake by dispersed cells from fresh female bovine anterior pituitary glands was examined, because we had interested in the mechanism of pituitary tumor regression following bromocriptine treatment and considered nucleic acid synthesis as an important process in the metabolism of these cells. The anterior pituitary cells were implanted on culture tubes using D-valine minimal essential medium with serum to suppress the overgrowth of fibroblasts and then maintained in L-valine Dulbecco's modified Eagle medium. (3H)-Uridine uptake by these cells was suppressed by bromocriptine, at-ergocriptine or ergotamine at a concentration varing from 10(-6) M to 10(-5) M, but not 10(-5) M of lergotrile. Among these alkaloids, bromocriptine had most strong inhibitory effect and suppressed the uptake to below 25% of control value at the concentration of 10(-5) M. Bromocriptine also inhibited the uptake of (3H)-thymidine, (3H)-cytidine, (3H)-adenosine or (3H)-guanosine in the same manner as (3H)-uridine. But neither (3H)-uracil, the base of uridine, nor (3H)-galactose uptake by cells was affected by bromocriptine. The incorporation of (3H)-uridine or (3H)-thymidine into TCA-insoluble fraction of the cells was also inhibited by bromocriptine as that in the total cells. It was suspected that bromocriptine acted on distinct transport site of both ribonucleoside and deoxyribonucleoside, because a high concentration (3.3 X 10(-5) M) of radio-inactive thymidine did not modify (3H)-uridine uptake by these cells as well as inhibitory effect of bromocriptine on it. These effect of bromocriptine were not blocked by haloperidol, known as dopamine antagonist, at the same concentration as bromocriptine, and dopamine had no effect on (3H)-uridine uptake by the cells. In addition, by adding 5 X 10(-4) M of dibutyryl cyclic AMP into the medium, the effect of bromocriptine was also not affected. These data suggest that the effect of bromocriptine on nucleoside transport in anterior pituitary cells may be dependent on the other binding site than D-2 dopamine receptor in the anterior pituitary cell membrane.