Dopamine withdrawal elicits prolonged calcium rise to support prolactin rebound release

Dopamine (DA) acts directly on pituitary lactotropes to inhibit the release of PRL. Removal of DA elicits a pronounced transient rise in PRL release to values exceeding pre-DA rates (PRL rebound). Electrophysiological studies have shown that lactotropes exhibit a period of increased Ca2+ action potential activity after DA withdrawal, leading to the proposal that enhanced Ca2+ influx during this period may support the rebound secretion of PRL. In the present studies, we investigated the effect of DA application and removal on the cytosolic free calcium concentration ([Ca2+]i) monitored by fura-2 in single rat lactotropes. Unchallenged lactotropes fell into two functionally distinct groups: those with stable [Ca2+]i that was not acutely sensitive to extracellular Ca2+, and those with spontaneous fluctuations in [Ca2+]i that were dependent upon influx of external Ca2+. There was striking variability in the [Ca2+]i patterns of the latter group, ranging from irregular, low amplitude fluctuations to rhythmic, repetitive oscillations with definable rise and decay kinetics. Application of DA resulted in a rapid decrease in [Ca2+]i concomitant with the cessation of these spontaneous [Ca2+]i fluctuations. After DA removal, these cells resumed oscillatory [Ca2+]i activities similar to those observed before DA application. In quiescent lactotropes, acute application of DA exerted no effect on resting [Ca2+]i, but quiescent cells could be activated to produce [Ca2+]i fluctuations by the application and withdrawal of DA. Again, the character of the induced [Ca2+] activity showed significant cell to cell variation. In contrast, the pattern of [Ca2+]i fluctuations was remarkably characteristic in a given cell in response to repeated challenges. A composite [Ca2+]i profile of 13 cells paralleled the PRL secretory rebound after application and removal of DA. The oscillatory rise in [Ca2+]i is functionally linked to the rebound release of PRL after DA removal, as both were immediately abolished by blockade of Ca2+ influx. These data demonstrate that the rebound secretion of PRL is dependent upon enhanced influx of extracellular Ca2+ after cells recover from DA-induced hyperpolarization and support the hypothesis that a population of inactivated Ca2+ channels has been recruited in response to application and withdrawal of DA.