Effects of commercial antiglaucoma drugs to glutamate-induced [Ca2+)]i increase in cultured neuroblastoma cells.
Over releasing of glutamate and cellular calcium influx always results in neuronal death. In the present study, we investigated various commercial antiglaucoma drugs including timolol (0.58 microM to 58 microM), betaxolol (1.62 microM to 162 microM), carteolol (6.8 microM to 680 microM), pilocarpine (4.08 microM to 408 microM), latanoprost (0.01 microM to 1.1 microM), dorzolamide (6.16 microM to 616 microM), brinzolamide (2.6 microM to 260 microM), brimonidine (0.68 microM to 68 microM), dipivefrin (0.28 microM to 28 microM) and preservative benzalkonium chloride on their effects to inhibit glutamate-induced intracellular free Ca(2+) ([Ca(2+)](i)) increase in cultured N1E-115 neuroblastoma cells. These drugs were diluted from original concentrations to 1/100, 1/1000 and 1/10000. The [Ca(2+)](i) mobility was studied after loading with fura-2-AM and analyzed by spectrofluorometry. It was found that betaxolol, dipivefrin and brimonidine have remarkable effects not only to inhibit the glutamate-induced [Ca(2+)](i) increase but also to decrease the basal [Ca(2+)](i). In the case of other drugs, only high concentration of timolol (58 microM) exhibited significant effect to completely prevent glutamate-induced [Ca(2+)](i) increase. Moreover, benzalkonium chloride did not exhibit any inhibitive effect. These results indicate that betaxolol, dipivefrin and brimonidine may have neuroprotective effects to inhibit the glutamate-induced over Ca(2+) influx damage.
Hong
Show-Jen
SJ
Department of Pharmacology, Kaohsiung Medical University, Taiwan. hong6657@ms5.hinet.net
Wu
Kwou-Yeung
KY
Wang
Hwei-Zu
HZ
Fong
Jim C
JC
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015784:Betaxolol / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000378:metabolism*; D002354:Carteolol / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005901:Glaucoma / Q000188:drug therapy; D018698:Glutamic Acid / Q000378:metabolism*; D000077338:Latanoprost; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010862:Pilocarpine / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D013999:Timolol / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000959:Antihypertensive Agents; D018696:Neuroprotective Agents; D011461:Prostaglandins F, Synthetic; D011810:Quinoxalines; D013449:Sulfonamides; D013843:Thiazines; D013876:Thiophenes; D010862:Pilocarpine; D018698:Glutamic Acid; D000068438:Brimonidine Tartrate; D000077338:Latanoprost; D013999:Timolol; D002354:Carteolol; C015173:dipivefrin; C111827:brinzolamide; C062765:dorzolamide; D015784:Betaxolol; D002118:Calcium; D004837:Epinephrine