TY - JOUR T1 - Modulation by LL-37 of the Responses of Salivary Glands to Purinergic Agonists JF - Molecular Pharmacology JO - Mol Pharmacol SP - 2037 LP - 2046 DO - 10.1124/mol.105.021444 VL - 69 IS - 6 AU - Stéphanie Pochet AU - Séverine Tandel AU - Stéphanie Querriére AU - Marie Tre-Hardy AU - Mikel Garcia-Marcos AU - Manuela De Lorenzi AU - Michel Vandenbranden AU - Aida Marino AU - Michel Devleeschouwer AU - Jean-Paul Dehaye Y1 - 2006/06/01 UR - http://molpharm.aspetjournals.org/content/69/6/2037.abstract N2 - The interaction of mice submandibular gland cells with LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES), a cationic peptide with immunomodulatory properties, was investigated. LL-37 at a concentration that did not affect the integrity of the cells increased the uptake of calcium and activated a calcium-insensitive phospholipase A2 (PLA2). The small release of ATP induced by LL-37 could not account for this stimulation because apyrase did not significantly block the response to LL-37. The divalent cation magnesium inhibited the response to LL-37, but this inhibition was probably nonspecific because it also inhibited the in vitro bacteriostatic effect of the peptide. The increase of calcium uptake by LL-37 was not affected by 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-62), a rather specific inhibitor of P2X7 receptors in mice. LL-37 also increased [Ca2+]i in cells from mice invalidated for these receptors. LL-37 had no effect on the response to carbachol. It inhibited the increase of [Ca2+]i and the activation of phospholipase D by ATP. It potentiated the activation of the PLA2 by the nucleotide. Finally, LL-37 increased the fluidity of the plasma membrane of submandibular gland cells. In conclusion, our results suggest that LL-37 is an autocrine regulator of submandibular gland cells. It does not stimulate mouse P2X7 receptors but modulates their responses. ER -