One minute of bromocriptine irreversibly inhibits prolactin release for hours

The ability of the dopamine receptor antagonist spiperone to block dopamine- or bromocriptine-inhibited prolactin release from dispersed rat anterior pituitary cells was tested in vitro. In a continuously perfused cell column apparatus, spiperone rapidly counteracted the inhibitory effect of dopamine but was unable to reverse the inhibitory effect of the potent dopamine agonist bromocriptine when added 30 min after bromocriptine. However, spiperone completely blocked the bromocriptine action if added simultaneously with bromocriptine. These basic data were confirmed, and the time relationships more accurately defined, in static incubations of monolayer cultures. Spiperone blocked the typical inhibition of prolactin release by bromocriptine only if the cells were pre- or coincubated with the antagonist. If spiperone was added as soon as 1 min after bromocriptine, the antagonist was unable to block the complete expression of the bromocriptine inhibition. These results suggest that bromocriptine is a functionally irreversible dopamine agonist for at least the 4 h of these studies.