DIFFERENTIAL EXPRESSION OF CALCITONIN AND PARATHYROID-HORMONE PARATHYROID HORMONE-RELATED PROTEIN RECEPTORS IN P19 EMBRYONIC CARCINOMA-CELLS TREATED WITH RETINOIC ACID

Mouse embryonic carcinoma P19 cell aggregates treated with retinoic ac id (RA) sequentially differentiate into neurons and astrocytes, wherea s attached cells develop a mesodermal phenotype. The expression of cal citonin (CT) and PTH/PTH-related protein (PTHrP) receptors was investi gated in embryonic cells, and during neural and mesodermal differentia tion. In embryonic P19 cells, specific binding of [I-125]salmon (s) CT (1-32) ([I-125]sCT(1-32)) was 56 fmol/mg protein, and of [I-125]chicke n (ch) [Tyr(36)]PTHrP(1-36) amide ([I-125]- chPTHrP(1-36)) < 0.5 fmol/ mg protein. Correspondingly, cAMP was maximally stimulated 47-fold by sCT(1-32) (EC50 0.05 nM) and 3-fold by chPTHrP(1-36) (EC50 1.3 nM). Re ceptor autoradiography revealed specific binding of [I-125]sCT(1-32) t o the undifferentiated P19 cells, but not to RA induced neurons and as trocytes. At the same time, [I-125]sCT(1-32) binding and cAMP accumula tion by sCT were gradually decreased. But, specific binding of [I-125] chPTHrP(1-36) was raised at least B-fold compared with embryonic cells to 3 fmol/mg protein, in parallel with a 10-fold higher maximal cAMP accumulation. A similar, but delayed suppression of CT and stimulation of PTH/PTHrP receptor expression was observed during mesodermal cell differentiation. The results indicate-that CT receptors are associated with undifferentiated P19 cells, whereas PTH/PTHrP receptors are expr essed in RA induced neural and mesodermal cells.