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

Pinolenic acid (PA), an 18 : 3 n-6 polyunsaturated fatty acid abundant in pine nut oil, is a structural isomer of γ-linolenic acid (GLA) and α-linolenic acid (ALA). Notably, GLA and ALA have been reported to inhibit prostanoid TP receptor–mediated vascular contraction. Whether PA similarly modulates TP receptor–dependent responses, however, remains unknown. In the present study, we investigated the effects of PA on TP receptor–mediated contraction in porcine coronary arteries (PCAs), TP receptor–evoked intracellular Ca2+ responses in human TP receptor–expressing cells, and its potential binding mode using molecular docking. In endothelium-denuded PCAs, PA (3–30 μM) concentration-dependently inhibited contractions induced by the TP receptor agonist U46619 and prostaglandin F2α (PGF2α), whereas it had little effect on contractions evoked by depolarization (high-KCl) or by other vasoactive agonists. PA caused a parallel rightward shift of the U46619 concentration–response curve, and Schild analysis yielded a slope not significantly different from unity; the corresponding pA2 value was 4.91. In human TP receptor–expressing 293T cells, PA significantly attenuated U46619-induced intracellular Ca2+ elevation, whereas it did not affect PGF2α-induced Ca2+ responses in prostanoid FP receptor–expressing cells. Docking simulations based on the human TP receptor crystal structure (Protein Data Bank ID: 8XJO) suggested that PA may occupy the orthosteric binding pocket, with its carboxylate group positioned near His89. Collectively, these findings suggest that PA inhibits TP receptor–mediated contraction and exhibits pharmacological properties consistent with competitive antagonism, supporting the concept that C18:3 fatty acids may modulate TP receptor signaling.