Stimulation of prolactin release by dopamine withdrawal: role of membrane hyperpolarization.
Hypothalamic dopamine (DA) tonically inhibits prolactin (PRL) release from the anterior pituitary gland, whereas removal of DA markedly augments its release to values exceeding pre-DA rates. We investigated whether electrical events induced by DA contribute to this secretory rebound. In primary cultured lactotropes, spontaneous Ca(2+)-dependent spiking activity was enhanced after recovery from DA-induced hyperpolarization. Voltage clamp studies showed a rapidly and a slowly inactivating Ca2+ current that were both augmented by a hyperpolarizing conditioning potential. We measured PRL release from perifused cells exposed to DA to correlate the electrical with the secretory responses. DA inhibited PRL release by 67%, whereas PRL secretion increased three- to fourfold over basal release after washout of DA. Valinomycin, used to directly hyperpolarize the cell membrane, mimicked the actions of DA, inhibiting PRL release (65%) and, upon washout, augmenting PRL secretion. Blocking the DA- or valinomycin-induced hyperpolarization by elevating external K+ concentration blocked both the inhibition and rebound of PRL release. These novel results demonstrate that hyperpolarization of the lactotrope membrane by DA is critical for the development of PRL rebound after DA withdrawal. We hypothesize the mechanism involves the removal of inactivation from a population of Ca2+ channels, leading to enhanced Ca2+ influx and PRL release upon recovery of the resting membrane potential after DA removal.
Department of Pediatrics, University of Maryland at Baltimore 21201.
K A
KA
Gregerson
N
N
Golesorkhi
R
R
Chuknyiska
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004298:Dopamine / Q000008:administration & dosage*; D004594:Electrophysiology; D005260:Female; D010904:Pituitary Gland, Posterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014634:Valinomycin / Q000494:pharmacology
D014634:Valinomycin; D011388:Prolactin; D004298:Dopamine