التفاصيل البيبلوغرافية
| العنوان: |
Human Ciliary Muscle Cell Responses to FP-Class Prostaglandin Analogs: Phosphoinositide Hydrolysis, Intracellular Ca[sup 2+] Mobilization and MAP Kinase Activation. |
| المؤلفون: |
Sharif, Naj A., Crider, Julie Y., Husain, Shahid, Kaddour-Djebbar, Ismail, Ansari, Habib R., Abdel-Latif, Ata A. |
| المصدر: |
Journal of Ocular Pharmacology & Therapeutics; Oct2003, Vol. 19 Issue 5, p437-455, 19p |
| مصطلحات موضوعية: |
MUSCLE cells, CELLS, PROSTAGLANDINS, HYDROLYSIS, PROTEIN kinases |
| مستخلص: |
Phospholipase C induced phosphoinositide (PI) turnover, intracellular Ca[sup 2+] ([Ca[sup 2+]]i) mobilization and mitogen-activated protein (MAP) kinase activation by FP-class prostaglandin analogs was studied in normal human ciliary muscle (h-CM) cells. Agonist potencies obtained in the PI turnover assays were: travoprost acid ((+)-fluprostenol; EC[sub 50] = 2.6 ± 0.8 nM) > bimatoprost acid (EC[sub 50] = 3.6 ± 1.2 nM) > (±)-fluprostenol (EC[sub 50] = 4.3 ± 1.3 nM) >> prostaglandin F[sup 2α] (PGF[sup 2α]) (EC[sub 50] = 134 ± 17 nM) > latanoprost acid (EC[sub 50] = 198 ± 83 nM) > S-1033 (EC[sub 50] = 2930 ± 1420 nM) > unoprostone (EC[sub 50] = 5590 ± 1490 nM) > bimatoprost (EC[sub 50] = 9600 ± 1100 nM). Agonist potencies in h-CM cells correlated well with those previously obtained for the cloned human ciliary body-derived FP receptor (r = 0.96, p< 0.001) and that present on h-TM cells (r = 0.94, p< 0.0001). Travoprost acid, PGF[sup 2α] and unoprostone also stimulated [Ca[sup 2+]]i mobilization in h-CM cells with travoprost acid being the most potent agonist. MAP kinase activity was stimulated in the h-CM cells with the following rank order of activity (at 100 nM): travoprost acid > PGF[sup 2α] > latanoprost acid > PGD[sup 2] > bimatoprost > latanoprost = bimatoprost acid = fluprostenol > PGE[sup 2] = S-1033 > unoprostone > PGI[sup 2]. The PI turnover, [Ca[sup 2+]]i mobilization and MAP kinase activation induced by several of these agonists was blocked by the FP receptor antagonist, AL-8810 (11β-fluoro-15-epiindanyl PGF[sup 2α]) (e.g. K[sup i] = 5.7 μ M versus PI turnover). These studies have characterized the biochemical and pharmacological properties of the native FP prostaglandin receptor present on h-CM cells using three signal transduction mechanism assays and a broad panel of FP-class agonist analogs (including free acids of bimatoprost, travoprost and latanoprost) and the FP receptor antagonist, AL-8810. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
