In:
Neuroendocrinology, S. Karger AG, Vol. 70, No. 1 ( 1999), p. 20-30
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 Ca 〈 sup 〉 2+ 〈 /sup 〉 channels can be involved in this potentiation. With a lactotropic cell line (GH 〈 sub 〉 4 〈 /sub 〉 C 〈 sub 〉 1 〈 /sub 〉 ) expressing human D 〈 sub 〉 2 〈 /sub 〉 -DA receptors, we tested the hypothesis that a brief escape from the tonic inhibitory action of DA triggers a facilitation of Ca 〈 sup 〉 2+ 〈 /sup 〉 influx through Ca 〈 sup 〉 2+ 〈 /sup 〉 channels. We initially found that in these cells, DA effectively and reversibly inhibited PRL secretion, and reversibly enhanced an inwardly rectifying K 〈 sup 〉 + 〈 /sup 〉 current. The effects of DA administration and withdrawal on Ca 〈 sup 〉 2+ 〈 /sup 〉 currents were examined using the patch-clamp technique in the whole-cell configuration and Ba 〈 sup 〉 2+ 〈 /sup 〉 as a divalent charge carrier through Ca 〈 sup 〉 2+ 〈 /sup 〉 channels. Macroscopic Ba 〈 sup 〉 2+ 〈 /sup 〉 currents were significantly decreased by short term (1–10 min) applications of DA (500 n 〈 i 〉 M 〈 /i 〉 ), which further declined following 24 h of constant exposure to DA. After DA removal, a biphasic facilitation of the density of Ba 〈 sup 〉 2+ 〈 /sup 〉 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 D 〈 sub 〉 2 〈 /sub 〉 -receptors expressed in GH 〈 sub 〉 4 〈 /sub 〉 C 〈 sub 〉 1 〈 /sub 〉 lactotrope cells causes an increase of high-voltage-activated Ca 〈 sup 〉 2+ 〈 /sup 〉 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.
Type of Medium:
Online Resource
ISSN:
0028-3835
,
1423-0194
Language:
English
Publisher:
S. Karger AG
Publication Date:
1999
detail.hit.zdb_id:
1483028-0
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