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Diacylglycerol-Containing Docosahexaenoic Acid in Acyl Chain Modulates Airway Smooth Muscle Tone

Département—Physiologie, Immunologie et Neurosciences, Unité Propre de Recherche de l'Enseignement Supérieur—Lipides et Nutrition, Faculté des Sciences de la Vie, Université de Bourgogne, Dijon, France; and Le Bilarium, Department of Physiology and Biophysics, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada

Correspondence and requests for reprints should be addressed to Professeur N. A. Khan, Directeur, Département—Physiologie, Immunologie et Neurosciences, UPRES Lipides et Nutrition, Faculté des Sciences de la Vie, 6 Boulevard Gabriel, 21000 Dijon, France. E-mail: naim.khan{at}u-bourgogne.fr

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.

Key Words: 1,2-dioctanoyl-sn-glycerol • calcium entry • docosahexaenoic acid • isometric tension • protein kinase C

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