Comparison of signalling mechanisms underlying UTP-evoked vasoconstriction of rat pulmonary and tail arteries

Tengah, Ampuan and Syed, Nawazish-i-Husain and Abdul Talip, Siti Tajidah and Bujang, Siti Nur Basirah and Kennedy, Charles (2018) Comparison of signalling mechanisms underlying UTP-evoked vasoconstriction of rat pulmonary and tail arteries. European Journal of Pharmacology, 837. pp. 45-52. ISSN 0014-2999 (https://doi.org/10.1016/j.ejphar.2018.08.031)

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Abstract

The endogenous nucleotide, UTP, acts at smooth muscle P2Y receptors to constrict rat pulmonary and tail arteries, but the underlying signalling pathways are poorly understood. The aim was to characterise the contribution of Ca2+ release and influx, rho kinase and protein kinase C to these contractions. Isometric tension was recorded from endothelium-denuded rat intralobar pulmonary and tail artery rings mounted on a wire myograph. Contractions were evoked by UTP and peak amplitude measured. Thapsigargin (1 µM), but not ryanodine (10 µM), significantly depressed contractions in both by 30-40% (P<0.05). Nifedipine (1 µM) significantly reduced contractions in tail artery by ~60% (P<0.01). Y27632 (10 µM), a rho kinase inhibitor and GF109203X (10 µM), a protein kinase C inhibitor, each significantly reduced pulmonary vasoconstriction by ~20%, and tail artery contractions by ~80% and ~40%, respectively (P<0.01). In pulmonary artery, Y27632, GF109203X and thapsigargin, acted in an additive manner, but nifedipine less so. Adding all four together abolished the UTP response. In tail artery, Y27632 plus thapsigargin or GF109203X or nifedipine abolished contractions. Thapsigargin, GF109203X and nifedipine, coapplied pair-wise, acted additively and applying all three together abolished UTP-evoked contractions. So, Ca2+ release from the sarcoplasmic reticulum and influx through Cav1.2 channels, but not ryanodine receptors, play significant roles in UTP-evoked vasoconstriction of rat pulmonary and tail arteries. Rho kinase and protein kinase C are also involved, but more so in tail artery. Thus UTP activates multiple signalling mechanisms that lead to vasoconstriction, but their relative importance differs in pulmonary compared with systemic arteries.

ORCID iDs

Tengah, Ampuan, Syed, Nawazish-i-Husain, Abdul Talip, Siti Tajidah, Bujang, Siti Nur Basirah and Kennedy, Charles ORCID logoORCID: https://orcid.org/0000-0001-9661-5437;
CORE (COnnecting REpositories)