Forskolin enhances calcium-evoked prolactin release from 7315c tumor cells without increasing the cytosolic calcium concentration.
The 7315c prolactin-secreting tumor cell was used as a model of a normal pituitary cell in order to study the enhancement by adenosine 3',5'-cyclic monophosphate (cAMP) of calcium-evoked hormone release. Forskolin and, by implication, cAMP had little effect on basal hormone release during a 10-min incubation period. Ionomycin and a high potassium concentration, treatments which enhanced the cytosolic calcium concentration, increased hormone release. When cells were exposed to forskolin prior to and during a challenge with either ionomycin or high potassium, a synergistic effect on prolactin release was observed. 8-Bromoadenosine 3',5'-cyclic monophosphate mimicked forskolin in enhancing ionomycin-evoked prolactin release while having little effect of its own on hormone release. Forskolin did not alter the increase in cytosolic calcium concentration elicited by either ionomycin or high potassium, nor did it increase the potency of ionomycin in enhancing prolactin release. The calcium channel antagonist, D-600, did not alter ionomycin-induced release or its enhancement by forskolin; D-600 blocked potassium-induced prolactin release. Ionomycin had no effect on basal cAMP synthesis by tumor cells and inhibited slightly the forskolin-induced increase in nucleotide synthesis. The results suggest that cAMP acts, at a site distal to the entry of calcium into the cytosol, to enhance the amount of prolactin released in response to an increase in the cytosolic calcium concentration.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000634:Aminoquinolines; D000818:Animals; D002118:Calcium / Q000032:analysis* / Q000502:physiology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D003600:Cytosol / Q000032:analysis*; D004987:Ethers / Q000494:pharmacology; D015759:Ionomycin; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011388:Prolactin / Q000276:immunology / Q000378:metabolism*; D051381:Rats
D000634:Aminoquinolines; D004987:Ethers; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015759:Ionomycin; D011388:Prolactin; D000242:Cyclic AMP; C035739:Quin2; D011188:Potassium; D002118:Calcium