Add time:07/15/2019         Source:sciencedirect.com

Bovine parathyroid hormone (PTH) 1–34 [bPTH(1–34)] and human PTH related protein [hPTHrP(1–34)] stimulated cAMP accumulation in opossum kidney (OK) cells with Km of 5 × 10−9M, but inhibition of phosphate uptake was obtained with 17-fold lower Km of 3 × 10−10M. Phosphate uptake was partially inhibited with [Nle8,18Tyr34]bPTH(3–34)NH2 without concomitant cAMP stimulation. With hPTHrP(7–34)NH2, cAMP accumulation was increased in parallel to inhibition of phosphate uptake. [D-Trp12Tyr34]bPTH(7–34)NH2 and [Tyr34]hPTH(7–34)NH2 had no agonist activity on cellular cAMP and inhibition of phosphate uptake. bPTH(1–34)-stimulated cAMP accumulation was antagonized by [Nle8,18Tyr34]bPTH(3–34)NH2, [D-Trp12Tyr34]bPTH (7–34)NH2, hPTHrP(7–34)NH2 and [Tyr34]hPTH(7–34)NH2 with Ki of 1.4 × 10−7, 2 × 10−7, 4.7 × 10−7 and 3.7 × 10−6M, respectively. But [Nle8,18Tyr34]bPTH(3–34)NH2 and [D-Trp12Tyr34]bPTH(7–34)NH2 reversed the inhibition of phosphate uptake only marginally, and hPTHrP(7–34)NH2 and [Tyr34]hPTH(7–34)NH2 were inactive. With hPTHrP(1–34) the Ki for cAMP accumulation of [Nle8,18Tyr34]bPTH(3–34)NH2 and hPTHrP(7–34)NH2 were 1.9 × 10−7 and 7.2 × 10−7M, and inhibition of phosphate uptake was partially reversed with [Nle8,18Tyr34]bPTH(3–34)NH2, but not with hPTHrP(7–34)NH2. The present results indicate that truncated hPTHrP(7–34)NH2, unlike [Tyr34]hPTH(7–34)NH2 and [D-Trp12Tyr34]bPTH(7–34)NH2, elevates cellular cAMP and inhibits phosphate uptake. bPTH(1–34)- and hPTHrP(1–34)-evoked cAMP accumulation is suppressed by PTH and PTHrP fragments while inhibition of phosphate uptake remains largely unaltered.

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