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Abstract #17501 Published in IGR 9-2
Cellular and molecular effects of unoprostone as a BK channel activator
Cuppoletti J; Malinowska DH; Tewari KP; Chakrabarti J; Ueno RBiochimica et Biophysica Acta - Biomembranes 2007; 1768: 1083-1092
Effects of unoprostone isopropyl (unoprostone), a prostaglandin metabolite analog; latanoprost, a PGF2α analog; and PGF2α were examined in HCN-1A cells, a model system for studies of large conductance Ca2+ activated K+(BK) channel activator-based neuroprotective agents. Unoprostone and latanoprost, both used as anti-glaucoma agents, have been suggested to act through FP receptors and have neuroprotective effects. Ion channel activation, plasma membrane polarization, Ca2+i changes and protection against long-term irreversible glutamate-induced Ca2+i increases were studied. Unoprostone activated iberiotoxin (IbTX)-sensitive BK channels in HCN-1A cells with an EC50 of 0.6 ± 0.2 nM and had no effect on Cl- currents. Unoprostone caused IbTX-sensitive plasma membrane hyperpolarization that was insensitive to AL8810, an FP receptor antagonist. In contrast, latanoprost and PGF2α activated a Cl- current sensitive to Ca2+i chelation, tamoxifen and AL8810, and caused IbTX-insensitive, AL8810-sensitive membrane depolarization consistent with FP receptor-mediated Ca2+ signaling Cl- current activation. Latanoprost and PGF2α, but not unoprostone, increased Ca2+i. Unoprostone, PGF2α only partially, but not latanoprost protected HCN-1A cells against glutamate-induced Ca2+ deregulation. These findings show that unoprostone has a distinctly different mechanism of action from latanoprost and PGF2α. Whether unoprostone affects the BK channel directly or an unidentified signaling mechanism has not been determined.
Dr. J. Cuppoletti, Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, P.O. Box 670576, Cincinnati, OH 45267-0576, USA. John.Cuppoletti@uc.edu
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
3.6 Cellular biology (Part of: 3 Laboratory methods)