The effects of rat parathyroid hormone-related protein (rPTHrP) and bovine and rat parathyroid hormone (bPTH and rPTH) on L-type Ca2+ channels in UMR 106 cells were investigated using the patch clamp technique. rPTHrP increased the whole cell L-type Ca2+ channel currents and the increase was concentration dependent. rPTHrP, at a concentration of 62.5 nM, increased the L-type Ca2+ channel current by 122+/-25%. bPTH was less potent. A concentration of 7.5 microM bPTH increased the current by 99+/-24%. Results obtained with rPTH were similar to those obtained using bPTH. Single channel measurements, using the cell-attached version of the patch clamp technique, showed an increase in both the number of channel openings and the mean open time when the cells were exposed to rPTHrP. This suggested that rPTHrP affected the gating of L-type Ca2+ channels in UMR 106 cells. This study demonstrates that the actions of bPTH and rPTHrP in UMR cells are mediated in part by extracellular Ca2+ entry. PTHrP, a paracrine agent important in development, is more potent in regulating Ca2+ entry than PTH.