title: The effects of prostaglandin analogues on intracellular Ca2+ in ciliary arteries of wild-type and prostanoid receptor-deficient mice.
abstract: OBJECTIVE
  To clarify the mechanism of prostaglandin (PG) analogue-dependent relaxation in ciliary arteries from wild-type (WT) and prostanoid receptor-deficient mice.
  
  
  METHODS
  The intracellular-free calcium concentration ([Ca(2+)](i)) in isolated WT mouse ciliary arteries was measured by fluorescence photometry. Reduction of [Ca(2+)](i) leading to vascular relaxation by PG analogues latanoprost, isopropyl unoprostone, or tafluprost was compared to the maximum increase of [Ca(2+)](i) by 50 mM KCl. The cyclooxygenase inhibitor indomethacin and the NO synthase inhibitor N(G)-nitro-(L)-arginine methylester ((L)-NAME) were added to investigate the involvement of vascular endothelial factors. Moreover, PG analogue-dependent reduction of [Ca(2+)](i) was measured in ciliary artery strips from FP, EP1, EP2, and EP3 receptor-deficient mice.
  
  
  RESULTS
  The 3 PG analogues reduced K(+)-dependent increase in [Ca(2+)](i) in a concentration-dependent manner. Indomethacin (10 μM) had little effect. The reductions of [Ca(2+)](i) induced by 10 μM PG analogues were not significantly affected by the treatment with the NO synthase inhibitor (L)-NAME (10(-4) M). The effect of all 3 PG analogues in FP and EP3 receptor-deficient arteries was similar to the effect in WT arteries. Latanoprost significantly enhanced the reduction of [Ca(2+)](i) in ciliary arteries from prostanoid EP1 and EP2 receptor-deficient mice compared to WT mice. Tafluprost had a similar effect in arteries from EP2 receptor-deficient mice.
  
  
  CONCLUSIONS
  PG analogues latanoprost, isopropyl unoprostone, and tafluprost reduced the K(+)-dependent increase in [Ca(2+)](i) in isolated mouse ciliary arteries. Endothelial-derived factors and FP and EP3 receptors were not involved in the responses. The increased effectiveness of latanoprost and tafluprost in reducing [Ca(2+)](i) in EP1 and EP2 receptor-deficient arteries suggests that the PG analogues may act, at least partially, through nonprostanoid receptor pathways. For glaucoma patients, PG analogues can be selected to reduce the intraocular pressure and increase the ocular blood flow.
authors.affiliation: Department of Ophthalmology, Akita University School of Medicine, Akita City, Japan. sanaeabe@med.akita-u.ac.jp
authors.forename: Sanae
authors.initials: S
authors.lastname: Abe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watabe
authors.forename: Sanae
authors.initials: S
authors.lastname: Takaseki
authors.forename: Makoto
authors.initials: M
authors.lastname: Aihara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshitomi
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D019842:Ciliary Arteries / Q000187:drug effects / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D042541:Intracellular Space / Q000378:metabolism; D000077338:Latanoprost; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology*; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000235:genetics; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000235:genetics; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000235:genetics; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000235:genetics
chemical_list: D000959:Antihypertensive Agents; D011460:Prostaglandins F; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; C034671:prostaglandin F2alpha receptor; C485333:tafluprost; C072630:isopropyl unoprostone; D000077338:Latanoprost; D015237:Dinoprost; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin