Potentiation of prolactin secretion following lactotrope escape from dopamine action - I. Dopamine withdrawal augments L-type calcium current

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 a s thyrotropin-releasing hormone (TRH). Previous evidence has suggested that modulation of Ca2+ channels can be involved in this potentiation. With a l actotropic cell line (GH(4)C(1)) expressing human D-2-DA receptors, we test ed the hypothesis that a brief escape from the tonic inhibitory action of D A triggers a facilitation of Ca2+ influx through Ca2+ channels. We initiall y found that in these cells, DA effectively and reversibly inhibited PRL se cretion, and reversibly enhanced an inwardly rectifying K+ current. The eff ects of DA administration and withdrawal on Ca2+ currents were examined usi ng the patch-clamp technique in the whole-cell configuration and Ba2+ as a divalent charge carrier through Ca2+ channels. Macroscopic Ba2+ currents we re significantly decreased by shortterm (1-10 min) applications of DA (500 nM), which further declined following 24 h of constant exposure to DA. Afte r DA removal, a biphasic facilitation of the density of Ba2+ currents was o bserved. An initial 2-fold enhancement of conductance was detected between 10 and 40 min, followed by a second facilitation of the same magnitude obse rved 24 h after DA withdrawal. The present results directly demonstrate tha t dissociation of DA from D-2-receptors expressed in GH(4)C(1) lactotrope c ells causes an increase of high-voltage-activated Ca2+ channel function, wh ich may play an important role in the cross-talking amplification of endocr ine cascades such as that involved in the TRH-induced PRL-release potentiat ing action of DA withdrawal.