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We examined the inhibitory effects of α-linolenic acid (ALA) on the contractions of pig coronary arteries. ALA concentration-dependently inhibited the contractions elicited by U46619 and prostaglandin F 2α without affecting those elicited by 80 mM KCl, histamine, acetylcholine, and serotonin. ALA rightward shifted the concentration-response curve of U46619, and Schild plot analysis revealed that ALA competitively antagonized U46619. Furthermore, ALA inhibited the increase in intracellular Ca 2+ concentration caused by TP receptor stimulation but not that caused by FP receptor stimulation. These results suggest that ALA behaves as a selective antagonist of TP receptors in coronary arteries., Competing Interests: Declaration of competing interest The authors indicated no potential conflicts of interest., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Objectives Dermatomyositis (DM) is often associated with fatal anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive rapidly progressive interstitial lung disease (RP-ILD). RP-ILD often fails to respond to intensive treatment and has a poor prognosis. We examined the effectiveness of early plasma exchange therapy plus intensive treatment with high-dose corticosteroids and multiple immunosuppressants. Methods Autoantibodies were identified by an immunoprecipitation assay and enzyme-linked immunosorbent assay. All clinical and immunological data were collected retrospectively from medical charts. We divided patients into two groups based on treatment regimen: intensive immunosuppressive therapy alone as initial treatment (IS group) and early initiation of plasma exchange (PE) plus intensive immunosuppressive therapy (ePE group). Early PE therapy was designated if PE therapy was initiated within two weeks of starting treatment. Comparisons of the treatment response and prognosis between groups were performed. Patients Anti-MDA5-positive DM with RP-ILD was screened. Results Forty-four RP-ILD and DM patients had anti-MDA5 antibodies. Four patients were excluded because they died before receiving sufficient combined immunosuppressive therapy or before the evaluation of the immunosuppressive treatment effectiveness (IS, n=31; ePE, n=9). All 9 patients in the ePE group had improved respiratory symptoms and were alive, whereas 12 of 31 patients in the IS group died (100 vs. 61%, p=0.037). Of the 8 patients who had 2 values for a poor prognosis, indicating the highest risk for death using the MCK model, 3 of 3 patients in the ePE group and 2 of 5 in the IS group were alive (100 vs. 40%, p=0.20). Conclusion The early initiation of ePE therapy plus intensive immunosuppressive therapy was effective for patients with DM and refractory RP-ILD.

This study was performed to elucidate whether eicosapentaenoic acid (EPA) suppresses spasm-prone blood vessel contractions induced by a thromboxane mimetic (U46619) and prostaglandin F 2α (PGF 2α ) and determine whether the primary target of EPA is the prostanoid TP receptor. Accordingly, we assessed: (1) the tension changes in porcine basilar and coronary arteries, and (2) changes in the Fura-2 (an intracellular Ca 2+ indicator) fluorescence intensity ratio at 510 nm elicited by 340/380 nm excitation (F340/380) in 293T cells expressing the human TP receptor (TP-293T cells) and those expressing the human prostanoid FP receptor (FP-293T cells). EPA inhibited both porcine basilar and coronary artery contractions induced by U46619 and PGF 2α in a concentration-dependent manner, but it did not affect the contractions induced by 80 mM KCl. EPA also inhibited the increase in F340/380 induced by U46619 and PGF 2α in TP-293T cells. In contrast, EPA showed only a marginal effect on the increase in F340/380 induced by PGF 2α in FP-293T cells. These findings indicate that EPA strongly suppresses the porcine basilar and coronary artery contractions mediated by TP receptor and that inhibition of TP receptors partly underlies the EPA-induced inhibitory effects on these arterial contractions., (© 2022. The Author(s).)

The inhibitory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and linoleic acid (LA) on the contractions induced by five prostanoids and U46619 (a TP receptor agonist) were examined in guinea pig gastric fundus smooth muscle (GFSM). Tension changes were isometrically measured, and the mRNA expression of prostanoid receptors was measured by RT-qPCR. DHA and EPA significantly inhibited contractions induced by the prostanoids and U46619, whereas LA inhibited those induced by prostaglandin D 2 and U46619. The mRNA expression levels of the prostanoid receptors were TP ≈ EP 3  >> FP > EP 1 . The inhibition by DHA, EPA, and LA was positively correlated with that by SQ 29,548 (a TP receptor antagonist) but not with that by L-798,106 (an EP 3 receptor antagonist). DHA and EPA suppressed high KCl-induced contractions by 35% and 25%, respectively, and the contractions induced by the prostanoids and U46619 were suppressed by verapamil, a voltage-dependent Ca 2+ channel (VDCC) inhibitor, by 40%-85%. Although LA did not suppress high KCl-induced contractions, it suppressed U46619-induced contractions in the presence of verapamil. However, LA did not show significant inhibitory effects on U46619-induced Ca 2+ increases in TP receptor-expressing cells. In contrast, LA inhibited U46619-induced contractions in the presence of verapamil, which was also suppressed by SKF-96365 (a store-operated Ca 2+ channel [SOCC] inhibitor). These findings suggest that the TP receptor and VDCC are targets of DHA and EPA to inhibit prostanoid-induced contractions of guinea pig GFSM, and SOCCs play a significant role in LA-induced inhibition of U46619-induced contractions., (© 2022 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)