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 as thyrotropin-releasing hormone (TRH). Previous evidence has suggested that modulation of Ca(2+) channels can be involved in this potentiation. With a lactotropic cell line (GH(4)C(1)) expressing human D(2)-DA receptors, we tested the hypothesis that a brief escape from the tonic inhibitory action of DA triggers a facilitation of Ca(2+) influx through Ca(2+) 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 Ca(2+) currents were examined using the patch-clamp technique in the whole-cell configuration and Ba(2+) as a divalent charge carrier through Ca(2+) channels. Macroscopic Ba(2+) 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 Ba(2+) 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(2)-receptors expressed in GH(4)C(1) lactotrope cells causes an increase of high-voltage-activated Ca(2+) 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.
del Mar Hernández
M
M
Neurobiology Center, National University of Mexico, Campus Juriquilla, Querétaro, Mexico.
García Ferreiro
R E
RE
García
D E
DE
Hernández
M E
ME
Clapp
C
C
Martínez de la Escalera
G
G
D000818:Animals; D001464:Barium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D004594:Electrophysiology; D007202:Indicators and Reagents; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011388:Prolactin / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D007202:Indicators and Reagents; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D001464:Barium; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D004298:Dopamine