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J. Biol. Chem., Vol. 263, Issue 18, 8557-8560, 06, 1988
H Juppner, AB Abou-Samra, S Uneno, WX Gu, JT Potts Jr and GV Segre
[Tyr36]human adenylate cyclase stimulating peptide (1-36)-NH2, an amino-
terminal analog of a tumor peptide which is associated with hypercalcemia
of malignancy, and [Nle8, Nle18, Tyr34]bovine parathyroid hormone
(PTH)-(1-34)-NH2 both bind with similar affinities to receptors on rat
osteosarcoma cells, ROS 17/2.8, when either of the peptides is used as the
radioligand. Pretreatment of the cells with either peptide down-regulates
available binding sites for either radioligand and desensitizes the cAMP
accumulation stimulated by either peptide. Prior exposure of the cells to
dexamethasone increases these responses to both peptides. Photoderivatized
radioiodinated [Tyr36]human adenylate cyclase-stimulating peptide
(1-36)-NH2 and [Nle8, Nle18, Tyr34]bovine PTH-(1-34)-NH2 both specifically
label a Mr = 80,000 membrane protein on ROS 17/2.8 cells. The intensity of
labeling this receptor band by either photoprobe is reduced by
co-incubation with either peptide over the same dose range. Equivalent
dose-dependent down-regulation of receptors which bind both photoprobes is
also found when ROS 17/2.8 cells are preincubated with either peptide.
Dexamethasone increases the intensity of receptor labeling. Our findings
strongly indicate that both peptides recognize the same plasma membrane
receptor on ROS 17/2.8 cells. Although the physiological function(s) of
human adenylate cyclase-stimulating peptide is unknown, these results could
explain why its biological actions on mineral ion metabolism so closely
simulate those of PTH and raise interesting questions about the general
biological and evolutionary significance of the use of the same receptor by
chemically distinct peptides.
The parathyroid hormone-like peptide associated with humoral hypercalcemia of malignancy and parathyroid hormone bind to the same receptor on the plasma membrane of ROS 17/2.8 cells
Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston 02114.
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