Stimulation of prolactin release by dopamine withdrawal: role of calcium influx.
Withdrawal of dopamine (DA), a neurotransmitter that inhibits prolactin (PRL) release from the anterior pituitary, stimulates PRL release with transient (30- to 45-min) secretory rates that exceed those observed before application of DA ("PRL rebound"). Using patch-clamp methods on identified rat lactotropes, we have demonstrated that a period of increased Ca(2+)-spiking activity follows recovery from the DA-induced hyperpolarization. The present experiments used dissociated pituitary cells to identify the relative roles of adenosine 3',5'-cyclic monophosphate (cAMP), inositol phosphates, and the enhanced influx of Ca2+ in the rebound secretion of PRL. Rebound secretion of PRL after DA withdrawal was completely blocked by the Ca2+ channel blocker verapamil (20 microM), which also inhibited spontaneous Ca(2+)-spiking activity. DA-induced changes in cAMP levels could be completely dissociated from the PRL rebound. Production of inositol phosphates rose after DA withdrawal but was secondary to the influx of Ca2+. These data demonstrate that influx of extracellular Ca2+ through verapamil-sensitive channels is a critical step in inducing PRL release after DA withdrawal. This finding supports our theory that DA-induced hyperpolarization recruits previously inactivated Ca2+ channels and upon DA washout the enhanced influx of Ca2+ through these voltage-regulated channels supports the rebound release of PRL.
Department of Pediatrics, University of Maryland at Baltimore 21201.
K A
KA
Gregerson
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R
Chuknyiska
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N
Golesorkhi
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000008:administration & dosage*; D005260:Female; D007295:Inositol Phosphates / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology
D007295:Inositol Phosphates; D011388:Prolactin; D014700:Verapamil; D000242:Cyclic AMP; D002118:Calcium; D004298:Dopamine