PMID- 15961724 OWN - NLM STAT- MEDLINE DCOM- 20051025 LR - 20161124 IS - 1044-1549 (Print) IS - 1044-1549 (Linking) VI - 33 IP - 4 DP - 2005 Oct TI - Diacylglycerol-containing docosahexaenoic acid in acyl chain modulates airway smooth muscle tone. PG - 378-86 AB - We synthesized and assessed the role of a diacylglycerol (DAG)-containing docosahexaenoic acid (DHA), that is, 1-stearoyl-2-docosahexaenoyl-sn-glycerol (SDHG), in the contraction of guinea pig airway smooth muscle (ASM). We compared its action with 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG) and 1,2-dioctanoyl-sn-glycerol (1,2-DiC8), a stable DAG analog. The three DAGs (SAG, SDHG, and 1,2-DiC8) induced reversible concentration-dependent contraction of ASM. SDHG induced higher guinea pig ASM contraction than did SAG and 1,2-DiC8. The effects of SDHG were blocked, to different extents, by nifedipine (L-type Ca2+ channel blocker). By employing GF-109203X (protein kinase C [PKC] inhibitor) and lanthanum (La3+), a nonselective cation channel blocker, we observed that SDHG evoked ASM contractile response via PKC-dependent and PKC-independent (but Ca2+-dependent) pathways. Interestingly, SAG exerted its action only by increasing [Ca2+]i and did not require PKC activation. To probe the implication of calcium mobilization, we employed thapsigargin (TG), which also induced ASM contraction in a calcium-dependent manner. SDHG and 1,2-DiC8, in a PKC-dependent manner, induced the phosphorylation of CPI-17 (myosin light chain phosphatase inhibitor of 17 kD). Furthermore, SAG and TG failed to phosphorylate CPI-17 in ASM cells. Our results suggest that different DAG species, produced during a dietary supplementation with fatty acids, could modulate the reactivity of airway smooth muscles in a PKC-dependent and -independent manner, and hence, may play a critical role in health and disease. FAU - Hichami, Aziz AU - Hichami A AD - Departement-Physiologie, Immunologie et Neurosciences, UPRES Lipides et Nutrition, Faculte des Sciences de la Vie, 21000 Dijon, France. FAU - Morin, Caroline AU - Morin C FAU - Rousseau, Eric AU - Rousseau E FAU - Khan, Naim A AU - Khan NA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050616 PL - United States TA - Am J Respir Cell Mol Biol JT - American journal of respiratory cell and molecular biology JID - 8917225 RN - 0 (Calcium Channel Blockers) RN - 0 (Diglycerides) RN - 0 (Enzyme Inhibitors) RN - 0 (Indoles) RN - 0 (Maleimides) RN - 25167-62-8 (Docosahexaenoic Acids) RN - EC 2.7.11.13 (Protein Kinase C) RN - I9ZF7L6G2L (Nifedipine) RN - L79H6N0V6C (bisindolylmaleimide I) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Bronchi/*anatomy & histology MH - Calcium/metabolism MH - Calcium Channel Blockers/pharmacology MH - Cells, Cultured MH - Diglycerides/chemistry/*metabolism MH - *Docosahexaenoic Acids/chemistry/metabolism MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Female MH - Guinea Pigs MH - Humans MH - In Vitro Techniques MH - Indoles/pharmacology MH - Male MH - Maleimides/pharmacology MH - Muscle Contraction/drug effects/physiology MH - Muscle, Smooth/drug effects/*physiology MH - Nifedipine/pharmacology MH - Phosphorylation MH - Protein Kinase C/antagonists & inhibitors/metabolism EDAT- 2005/06/18 09:00 MHDA- 2005/10/26 09:00 CRDT- 2005/06/18 09:00 PHST- 2005/06/18 09:00 [pubmed] PHST- 2005/10/26 09:00 [medline] PHST- 2005/06/18 09:00 [entrez] AID - 2005-0136OC [pii] AID - 10.1165/rcmb.2005-0136OC [doi] PST - ppublish SO - Am J Respir Cell Mol Biol. 2005 Oct;33(4):378-86. doi: 10.1165/rcmb.2005-0136OC. Epub 2005 Jun 16.