Dependence of prolactin release on coupling between Ca(2+) mobilization and voltage-gated Ca(2+) influx pathways in rat lactotrophs.
Two Ca(2+)-mobilizing receptors expressed in lactotrophs, endothelin-A (ET(A)) and thyrotropin-releasing hormone (TRH), induce a rapid Ca(2+) release from intracellular stores and prolactin (PRL) secretion but differ in their actions during the sustained stimulation; TRH facilitates and ET-1 inhibits voltage-gated calcium influx (VGCI) and PRL secretion. In pertussis toxin (PTX) treated cells, ET-1-induced inhibition of VGCI was abolished and the pattern of Ca(2+) signaling was highly comparable with that observed in TRH-stimulated cells. The addition of Cs(+), a relatively specific blocker of inward rectifier K(+) channels, mimicked the effect of PTX on the pattern of ET-1-induced sustained Ca(2+) signaling, but only in about 50% of cells, and did not affect agonist-induced inhibition of PRL secretion. Extracellular Cs(+) was also ineffective in altering the TRH-induced facilitation of VGCI and PRL secretion. Furthermore, apamin and paxilline, specific blockers of Ca(2+)-activated SKand BK-type K(+) channels, respectively; E-4031, a blocker of ether a-go-go K(+) channel; and linopirdine, a blocker of M-type K(+) channel, did not affect the agonist-specific patterns of calcium signaling and PRL secretion. These results suggest that ET-1 inhibits VGCI through activation of Cs(+)-sensitive channels, presumably the Gi/o-controlled inward rectifier K(+) channels, and that this agonist also inhibits PRL release, but downstream of Ca(2+) influx. Further studies are required to identify the mechanism of sustained TRH-induced facilitation of VGCI and PRL secretion.
Tomić
Melanija
M
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Development, National Institutes of Health, Bethesda, MD 20892-4510, USA.
Andric
Silvna A
SA
Stojilkovic
Stanko S
SS
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D037342:Pertussis Toxin / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D015220:Calcium Channels; D019332:Endothelin-1; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D044022:Receptor, Endothelin A; D002586:Cesium; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D037342:Pertussis Toxin; D002118:Calcium