Picture of neon light reading 'Open'

Discover open research at Strathprints as part of International Open Access Week!

23-29 October 2017 is International Open Access Week. The Strathprints institutional repository is a digital archive of Open Access research outputs, all produced by University of Strathclyde researchers.

Explore recent world leading Open Access research content this Open Access Week from across Strathclyde's many research active faculties: Engineering, Science, Humanities, Arts & Social Sciences and Strathclyde Business School.

Explore all Strathclyde Open Access research outputs...

Involvement of rho-kinase in contraction of guinea-pig aorta induced by prostanoid eP3 receptor agonists

Shum, W.W.C. and Le, G.Y. and Jones, R.L. and Gurney, A.M. and Sasaki, Y. (2003) Involvement of rho-kinase in contraction of guinea-pig aorta induced by prostanoid eP3 receptor agonists. British Journal of Pharmacology, 139 (8). pp. 1449-1461. ISSN 1476-5381

Full text not available in this repository. Request a copy from the Strathclyde author


The mechanism of contraction of guinea-pig isolated aorta induced by the prostanoid EP3 receptor agonist sulprostone (0.1–300 nm) has been investigated. In 60% of the experiments, the sulprostone log concentration–response curve (maximum=15–40% of 100 nm U-46619 response; low-responders) was unaffected by the removal of extracellular Ca2+, blockade of L-type Ca2+ channels with nifedipine and depletion of internal Ca2+ stores. In the remaining preparations (35–65% of 100 nm U-46619 response; high-responders), contractions to higher sulprostone concentrations showed a nifedipine-sensitive component, which was enhanced by charybdotoxin. In Ca2+-free Krebs solution, established contractions to 300 nm sulprostone were abolished by the Rho-kinase inhibitors H-1152, Y-27632 and HA-1077 (IC50 values=190, 770 and 2030 nm). The PKA/Rho-kinase inhibitor H-89 (10 nm–10 μm) caused enhancement progressing to inhibition. The selective PKC inhibitor Ro 32-0432 (3 μm) had no effect, while staurosporine, recently shown to be a potent Rho-kinase inhibitor, abolished sulprostone responses (IC50 ∼47 nm), but its action was slow. The MAP kinase inhibitors SB 202190, SB 203580 and PD 80958 produced little inhibition. In normal Krebs solution, H-1152 and Y-27632 abolished established contractions to 300 nm sulprostone and 1 μm phenylephrine, and partially inhibited 10 μm phenylephrine and 50 mm K+ responses. The results are discussed in relation to the reported potencies of the protein kinase inhibitors in enzyme assays. Activation of the Rho-kinase pathway appears to be a primary mechanism of contraction induced by EP3 receptor agonists in guinea-pig aorta.