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- Title
cGMP-mediated calcium desensitisation of pulmonary artery does not involve Rho kinase or PKG: role for PKA.
- Authors
Ward, Jeremy P. T.; De Silva, Anushika; Aaronson, Philip I.
- Abstract
Vasodilators that increase cGMP reduce Ca2+ sensitivity as well as Ca2+, and may inhibit the RhoA/Rho kinase pathway. We examined cGMP-mediated Ca2+ desensitisation using 8-Br-cGMP, in rat or-toxin permeabilized intrapulmonary arteries (IPA). In IPA contracted by raising Ca2+, 8-Br-cGMP relaxed IPA with an EC50 of ∼25nM. Surprisingly, the Rho kinase inhibitor Y-27632 (10µM) had no significant effect. Consistent with this, 100nM 8-Br-eGMP caused a significant shift in the Ca2+ response curve (EC50 Control: 157 ± 23 nM; 8-Br-cGMP: 252 ± 47 nM); although Y-27632 also increased the EC50 (204 ± 26 nM), in its presence 8-Br-cGMP still caused a further increase (306 ± 45nM). Similar results were obtained with PGF2α, which activates Rho kinase. The effects of 8-Br-cGMP were not inhibited by KT5823, a PKG inhibitor, but were by H89, a PKA inhibitor. Similarly, Rp-8-Br-cAMP (25 µM) depressed 8-Br-cGMP-mediated relaxation at pCa 6.8 from 76.9 ± 2.5% to 43.1 ± 4.5%. 8-Br-cGMP had a greater effect on MLC phosphorylation than on that of MYPT1. This suggests 8-Br-cGMP reduces Ca2+ sensitivity in IPA via PKA, possibly involving its target teleokin which affects myosin phosphatase.
- Subjects
PULMONARY artery; VASODILATORS; PHOSPHORYLATION; PHOSPHATASES; CARDIOVASCULAR agents
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA1439
- ISSN
0892-6638
- Publication type
Article