Haloperidol causes irreversible damage to rat anterior pituitary lactotropes in culture.
Haloperidol, in concentrations in excess of 10(-5)M promotes the release of prolactin from rat anterior pituitary cells in monolayer culture. Histologic evidence revealed that 10(-4)M concentrations cause an irreversible cytotoxic effect that resulted in a loss of cell membrane integrity and a massive release of intracellular prolactin into the surrounding medium. Paradoxically, at 10(-5)M, haloperidol significantly inhibited prolactin release and promoted an accumulation of intracellular secretory granules. Lower concentrations had no significant effect. Although it is nominally classified as a dopamine receptor blocker and can (in lower concentrations) inhibit dopamine's suppression of prolactin release, haloperidol in higher concentration enhances prolactin release by a cytotoxic mechanism unrelated to dopamine receptor interaction.
D000818:Animals; D002478:Cells, Cultured; D006220:Haloperidol / Q000633:toxicity*; D008855:Microscopy, Electron, Scanning; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D011388:Prolactin; D006220:Haloperidol