Domperidone induces a probenecid-sensitive rise in immunoreactive prolactin in cerebroventricular perfusates in female rats.
The present study examined immunoreactive prolactin (ir-PRL) access into the cerebrospinal fluid (CSF) by monitoring ir-PRL levels in the blood and cerebroventricular perfusates of ovariectomized (ovx) rats treated with the dopamine antagonist, domperidone (DOMP). In Expt. 1 PRL plasma levels were measured in rats treated with DOMP i.p. (2.5, 5.0 and 10.0 mg/kg). All doses of DOMP significantly increased PRL plasma levels. In Expt. 2 animals were treated i.p. with DOMP (10 mg/kg) or DOMP plus the active transport blocking agent, probenecid (PROB; 250 mg/kg). Plasma PRL and ir-PRL in cerebroventricular perfusates were measured in separate sets of animals using catheters and a push-pull perfusion system, respectively. DOMP induced an increase in plasma PRL that was followed 30-40 min later by a rise in ventricular perfusates ir-PRL levels. PROB treatment induced a greater increase in plasma PRL levels in DOMP-treated animals, but delayed the DOMP-induced increase in ir-PRL ventricular perfusate ir-PRL levels. The delay in the rise of ir-PRL in ventricular perfusates observed in rats treated with DOMP plus PROB may be due to a PROB's interference with the transport of PRL from the blood into CSF. These results suggest that under some conditions ir-PRL in CSF originates from the pituitary.
Felicio
L F
LF
Department of Anatomy and Cell Biology, Harvard Medical School, Boston, MA 02115.
Bridges
R S
RS
D000818:Animals; D001812:Blood-Brain Barrier; D002552:Cerebral Ventricles / Q000378:metabolism*; D004294:Domperidone / Q000494:pharmacology*; D005260:Female; D008297:Male; D010052:Ovariectomy; D010477:Perfusion; D011339:Probenecid / Q000494:pharmacology*; D011388:Prolactin / Q000096:biosynthesis* / Q000134:cerebrospinal fluid / Q000276:immunology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques
D004294:Domperidone; D011388:Prolactin; D011339:Probenecid