Pinolenic Acid Inhibits Prostanoid TP Receptor-Mediated Contraction in Porcine Coronary Arteries

Area of Science:

• Biochemistry
• Pharmacology
• Cardiovascular Research

Background:

• Pinolenic acid (PA) is a polyunsaturated fatty acid structurally similar to gamma-linolenic acid (GLA) and alpha-linolenic acid (ALA).
• GLA and ALA are known to inhibit prostanoid TP receptor-mediated vascular contraction.
• The TP receptor modulating effects of PA remain largely uncharacterized.

Purpose of the Study:

• To investigate the effects of PA on TP receptor-mediated contraction in porcine coronary arteries (PCAs).
• To examine TP receptor-evoked intracellular Ca2+ responses in human TP receptor-expressing cells.
• To elucidate the potential binding mode of PA to the TP receptor using molecular docking.

Main Methods:

• Concentration-dependent inhibition of U46619 and prostaglandin F2α (PGF2α)-induced contractions in endothelium-denuded PCAs.
• Assessment of intracellular Ca2+ responses in human TP receptor-expressing 293T cells.
• Molecular docking simulations using the human TP receptor crystal structure (PDB ID: 8XJO).

Main Results:

• PA (3-30 μM) concentration-dependently inhibited TP receptor agonist U46619-induced contractions in PCAs.
• PA exhibited competitive antagonism of TP receptor-mediated contraction (pA2 = 4.91).
• PA attenuated U46619-induced intracellular Ca2+ elevation in human TP receptor-expressing cells but not PGF2α-induced responses in FP receptor cells.

Conclusions:

• Pinolenic acid acts as a TP receptor antagonist, inhibiting TP receptor-mediated vascular contraction.
• PA's pharmacological profile suggests competitive antagonism at the TP receptor.
• These findings support the role of C18:3 fatty acids in modulating TP receptor signaling pathways.