Phosphoinositide hydrolysis in response to the withdrawal of dopamine inhibition in enriched lactotrophs in culture.
The formation of inositol phosphates and hydrolysis of polyphosphoinositides in response to DA addition or removal was studied in cultured anterior pituitary cells from E2-treated rats. The cells were incubated for 24 h with [3H]inositol to label the polyphosphoinositides either with or without DA (500 nM) in the medium. [3H]inositol phosphate and [3H]polyphosphoinositide levels were determined by anion-exchange chromatography after KOH deacylation of the latter. Acute (5 min) administration of DA to cells cultured without DA resulted in no change in the levels of [3H]inositol phosphates but a significant increase (50 +/- 10%) in the levels of [3H]polyphosphoinositides. Similarly, tonic exposure to DA for 40 h resulted in an increase (127 +/- 9%) of [3H]polyphosphoinositide levels. Acute withdrawal of DA from the medium for 5 min induced a 77 +/- 9% increase in the levels of [3H]inositol phosphate and a 27 +/- 3% decrease in [3H]polyphosphoinositide levels. These results suggest that the inositol phosphate messenger system of lactotrophs is negatively coupled to DA receptors. The efficiency of dopamine removal to activate this pathway is consistent with the kinetics of DA binding to its receptor and observations that DA removal is an important physiological signal for PRL release.
de la Escalera
G M
GM
Reproductive Endocrinology Center, University of California, San Francisco.
Martin
T F
TF
Weiner
R I
RI
D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013403:Sugar Phosphates / Q000378:metabolism*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D013403:Sugar Phosphates; D004298:Dopamine