Selective effects of hyperprolactinemia on in vitro dopamine release from median eminence synaptosomes.
Prolactin is thought to exert an autoregulatory, negative feedback effect on its own secretion via stimulation of the tuberoinfundibular dopaminergic (TIDA) neurons. To investigate possible mechanisms involved in this feedback, the effects of experimentally induced hyperprolactinemia on the release of 3H-dopamine (3H-DA) were studied in nerve terminals (synaptosomes) isolated from rat median eminence (ME), the TIDA neuronal projection field. Synaptosomes were prepared from adult male rats treated with ovine prolactin (oPRL) or the vehicle for 48 hr. Synaptosomes were incubated in 0.1 microM 3H-DA at 30 degrees C until steady-state conditions were achieved, and then release of the preaccumulated transmitter was measured over 1-20 sec time intervals under basal and depolarizing conditions. Release of 3H-DA elicited by depolarization of the terminals was significantly greater in ME synaptosomes prepared from oPRL-treated animals as compared with preparations from controls. This effect of the hyperprolactinemia appeared to be specific to the TIDA neurons since oPRL treatment did not result in increased evoked release of 3H-DA from terminals prepared from the mesolimbic, tuberohypophyseal, or nigrostriatal dopaminergic neurons. Basal efflux in all preparations was not changed from controls. The increased evoked release in oPRL-treated ME occurred when depolarization was induced either with high external [KCl] or veratridine. The enhanced 3H-DA efflux was evident during depolarization over a wide range of external calcium concentrations (0.01-3.0 mM), in the presence of 20 nM Ni2+ to block Ca2+ influx through voltage-gated channels, or when all external Ca2+ had been chelated, indicating that this effect of oPRL involves DA released through a mechanism independent of external calcium.
Gregerson
K A
KA
Department of Physiology, University of Maryland, School of Medicine, Baltimore 21201.
Selmanoff
M
M
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism / Q000648:ultrastructure; D004298:Dopamine / Q000378:metabolism*; D006966:Hyperprolactinemia / Q000378:metabolism*; D008297:Male; D008473:Median Eminence / Q000378:metabolism* / Q000648:ultrastructure; D009919:Orchiectomy; D011189:Potassium Chloride / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012756:Sheep; D013574:Synaptosomes / Q000378:metabolism*; D013997:Time Factors
D011189:Potassium Chloride; D011388:Prolactin; D002118:Calcium; D004298:Dopamine