Abstract
Purpose: :
To investigate the effects of prostaglandin (PG) receptor agonists of the FP–class, EP–class, TP–class and DP–class on MLC phosphorylation, p42/p44 MAP kinase phosphorylation and contraction in the iris sphincter of bovine and cat.
Methods: :
Three signal transduction mechanism assays, namely MLC phosphorylation, MAP kinase phosphorylation and contraction were employed in this study.
Results: :
We demonstrated that in bovine iris sphincter the rank order of potency of the PG agonists in the contractile and MLC phosphorylation assays is as follows: E2 > U46619 > F2α > D2, and in cat F2α > D2 > E2 > U46619. In the MAP kinase assay, in bovine iris sphincter the rank order of potency is E2 > F2α and in cat F2α > E2. These conclusions are supported by the following findings: (1) In the contractile assay, in the bovine sphincter the EC50s for PGF2α, PGE2, U46619 and PGD2 were found to be 1.4 x 10–7, 5.0 x 10–9, 9.0 x 10–9 and 1.3 x 10–6 M, respectively, and the corresponding values in the cat were 1.9 x 10–8, 2.3 x 10–7, 1.5 x 10–6 and 6.9 x 10–8 M, respectively. (2) In the MLC phophorylation assay, in the bovine sphincter PGF2α, PGE2, U46619 and PGD2 increased MLC phophorylation by 118, 165, 153 and 72% respectively, and the corresponding values in cat were 175, 99, 90 and 95%, respectively. (3) In the MAP kinase assay, in the bovine iris sphincter PGF2α and PGE2, increased MAP kinase phosphorylation by 276 and 328%, respectively, and the corresponding values in cat were 308 and 245%, respectively.
Conclusions: :
The data presented demonstrate pronounced species differences in the effects of the prostanoids on the MLC kinase signaling pathway in bovine and cat irides and furthermore confirm the existence of FP–receptors in that of the bovine. EP–receptor ligands are strong agonists in bovine sphincter whereas FP–receptor ligands are strong agonists in cat iris sphincter .
Keywords: eicosanoids • receptors • iris