Potentiation of Prolactin Secretion following Lactotrope Escape from Dopamine Action

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Abstract
Hypothalamic dopamine (DA) tonically inhibits prolactin (PRL) release from the anterior pituitary gland. Transient escapes from this DA tone elicit a pronounced potentiation of the PRL-releasing action of secretagogues such as thyrotropin-releasing hormone (TRH). Previous evidence has suggested that modulation of Ca2+ channels can be involved in this potentiation. With a lactotropic cell line (GH4C1) expressing human D2-DA receptors, we tested the hypothesis that a brief escape from the tonic inhibitory action of DA triggers a facilitation of Ca2+ influx through Ca2+ channels. We initially found that in these cells, DA effectively and reversibly inhibited PRL secretion, and reversibly enhanced an inwardly rectifying K+ current. The effects of DA administration and withdrawal on Ca2+ currents were examined using the patch-clamp technique in the whole-cell configuration and Ba2+ as a divalent charge carrier through Ca2+ channels. Macroscopic Ba2+ currents were significantly decreased by short term (1–10 min) applications of DA (500 nM), which further declined following 24 h of constant exposure to DA. After DA removal, a biphasic facilitation of the density of Ba2+ currents was observed. An initial 2-fold enhancement of conductance was detected between 10 and 40 min, followed by a second facilitation of the same magnitude observed 24 h after DA withdrawal. The present results directly demonstrate that dissociation of DA from D2-receptors expressed in GH4C1 lactotrope cells causes an increase of high-voltage-activated Ca2+ channel function, which may play an important role in the cross-talking amplification of endocrine cascades such as that involved in the TRH-induced PRL-release potentiating action of DA withdrawal.