Novel structurally altered P-2X1 receptor is preferentially activated by adenosine diphosphate in platelets and megakaryocytic cells

Experimental and clinical data suggest the presence of multiple types of ad enosine diphosphate (ADP) receptors, one coupled to ligand-gated cation cha nnels (P-2X) and others coupled to G-protein-coupled (P-2Y) receptors, This report identifies cDNA for a structurally altered P-2X1- like receptor in megakaryocytic cell lines (Dami and CMK 11-5) and platelets that, when tran sfected into nonresponsive 1321 cells, confers a specific sensitivity to AD P with the pharmacologic rank order of ADP > > ATP > > > alpha,beta -methyl ene-ATP as measured by Ca++ influx This receptor (P-2X1del) contains a dele tion of 17 amino acids (PALLREAENFTLFIKNS) that includes an NFT consensus s equence for N-linked glycosylation. Glycosylated forms of the P-2X1del and P-2X1wt receptors were indistinguishable electrophoretically by Western blo t or by immunoprecipitation using available antihuman and antirat antibodie s. These results indicate that the expression of the P-2X1del receptor resu lts in an influx of Ca++ induced by ADP, Expression of P-2X1del receptor ho momeric subunits is sufficient to express a receptor preferentially activat ed by ADP and suggests that this altered form, alone or in combination with P-2X1wt receptors, is a component of an ADP-activated ion channel. (C) 200 1 by The American Society of Hematology.