Melanocortin (MC) 3-MSH (Melanocyte-Stimulating Hormone) is believed to signal through the MC 3 receptor. It induces a sustained increase in intracellular free calcium levels ([Ca2+]i) in a subpopulation of pituitary cells. Most of the cells responding to 3-MSH express more than one pituitary hormone mRNA. The effect of 3-MSH is blocked by SHU9119, a MC3R and MC4R antagonist, in only 50% of the responsive cells, suggesting that in half of these cells the mediating receptor is not the MC3R. Low picomolar doses of 3-MSH increase [Ca2+]i in the growth hormone (GH)- and prolactin (PRL)-secreting GH3 cell line.