In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 11 ( 2022-11-17), p. e0265854-
Abstract:
Diabetes mellitus is a chronic metabolic disorder which induces endothelial dysfunction and platelet activation. Eicosanoids produced from arachidonic acid regulate cellular and vascular functions. Sigma-1 receptors (S1R) are expressed in platelets and endothelial cells and S1R expression is protective in diabetes. Objectives Our aim was to examine the influence of sub-chronic, in vivo administered S1R ligands PRE-084, (S) -L1 (a new compound) and NE-100 on the ex vivo arachidonic acid metabolism of platelets and aorta in streptozotocin-induced diabetic rats. Methods The serum level of the S1R ligands was detected by LC-MS/MS before the ex vivo analysis. Sigma-1 receptor and cyclooxygenase gene expression in platelets were determined by RT-qPCR. The eicosanoid synthesis was examined with a radiolabelled arachidonic acid substrate and ELISA. Results One month after the onset of STZ-induced diabetes, in vehicle-treated, diabetic rat platelet TxB 2 and aortic 6-k-PGF 1α production dropped. Sub-chronic in vivo treatment of STZ-induced diabetes in rats for one week with PRE-084 enhanced vasoconstrictor and platelet aggregator and reduced vasodilator and anti-aggregator cyclooxygenase product formation. (S) -L1 reduced the synthesis of vasodilator and anti-aggregator cyclooxygenase metabolites and promoted the recovery of physiological platelet function in diabetic rats. The S1R antagonist NE-100 produced no significant changes in platelet arachidonic acid metabolism. (S) -L1 decreased the synthesis of vasoconstrictor and platelet aggregator cyclooxygenase metabolites, whereas NE-100 increased the quantity of aortic vasodilator and anti-aggregator cyclooxygenase products and promoted the recovery of diabetic endothelial dysfunction in the aorta. The novel S1R ligand, (S) -L1 had similar effects on eicosanoid synthesis in platelets as the agonist PRE-084 and in aortas as the antagonist NE-100. Conclusions S1R ligands regulate cellular functions and local blood circulation by influencing arachidonic acid metabolism. In diabetes mellitus, the cell-specific effects of S1R ligands have a compensatory role and aid in restoring physiological balance between the platelet and vessel.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0265854
DOI:
10.1371/journal.pone.0265854.g001
DOI:
10.1371/journal.pone.0265854.g002
DOI:
10.1371/journal.pone.0265854.g003
DOI:
10.1371/journal.pone.0265854.g004
DOI:
10.1371/journal.pone.0265854.g005
DOI:
10.1371/journal.pone.0265854.g006
DOI:
10.1371/journal.pone.0265854.g007
DOI:
10.1371/journal.pone.0265854.g008
DOI:
10.1371/journal.pone.0265854.g009
DOI:
10.1371/journal.pone.0265854.g010
DOI:
10.1371/journal.pone.0265854.t001
DOI:
10.1371/journal.pone.0265854.s001
DOI:
10.1371/journal.pone.0265854.s002
DOI:
10.1371/journal.pone.0265854.s003
DOI:
10.1371/journal.pone.0265854.s004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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