EXTRACELLULAR ATP AS AN AUTOCRINE PARACRINE REGULATOR OF PROLACTIN-RELEASE/

Recent evidence demonstrates that ATP, costored with a number of hormo nes and neurotransmitters in secretory granules, is coreleased during exocytosis of these agents. Here, we explored the possibility that ext racellular ATP subserves an autocrine and/or paracrine role in the reg ulation of prolactin (PRL) release by subjecting rat pituitary cells t o various experimental manipulations aimed at evaluating putative inte ractions between ATP and mammotropes. Our results strongly support the view that ATP functions as a local regulator of PRL secretion. To be more specific, we observed that ATP is released in a predictable manne r by physiologically relevant secretagogues that are reasonably target ed to mammotropes. Moreover, we found that ATP can act directly on pit uitary cells to stimulate the release of PRL from most (if not all) ma mmotropes. Finally, we determined that antagonism or removal of ATP le ads to a diminution of PRL export from pituitary cells cultured under basal or thyrotropin-releasing hormone-stimulated conditions. On the b asis of these results, we propose that ATP acts locally to amplify and prolong the PRL secretory response elicited by a more traditional hyp ophysiotropic signal.