Role of changes in membrane lipid structure in the action of 1,25-dihydroxyvitamin D3.

Recent studies have shown that 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) stimulates the entry of calcium into the duodenal mucosal cell of the chick by a mechanism that does not require the synthesis of new protein. Using isolated brush border membrane vesicles (BBMV) from these cells, we have explored the mechanism by which 1,25-(OH)2-D3 acts. Administration of the hormone leads to an increase in calcium uptake into BBMV. This calcium uptake is a saturable process. Addition of the methyl ester of cis-vaccenic acid to BBMV in vitro leads to a specific increase in calcium uptake into vesicles from vitamin D-deficient chicks but not in those from 1,25-(OH)2-D3-treated chicks. Administration of 1,25-(OH)2-D3 leads to an increase in the de novo synthesis of phosphatidylcholine (PC) and an increase in the total PC content of the brush border membrane. It also increases the turnover of fatty acids into PC, which results in an increase in the content of polyunsaturated fatty acids in the PC fraction. These changes in lipid structure and turnover either precede in time or occur simultaneously with the change in calcium transport rate, and neither is blocked by the administration of cycloheximide. It is proposed that the primary mechanism by which 1,25-(OH)2-D3 regulates calcium transport across the luminal membrane of the enterocyte is by inducing a specific alteration in membrane PC content and structure, which leads to an increase in membrane fluidity and thereby to an increase in calcium transport rate.