title: Selective inhibition of thapsigargin-induced contraction and capacitative calcium entry in mouse anococcygeus by trifluoromethylphenylimidazole (TRIM).
abstract: This study examined the effects of trifluoromethylphenylimidazole (TRIM) on tone, and calcium entry, in mouse anococcygeus stimulated by either thapsigargin (Tg; 100 nM) which activates capacitative calcium entry (CCE), or high K (60 mM) which activates voltage-operated calcium channels. TRIM (1 - 333 microM) produced concentration-related relaxation of Tg-induced tone (EC(50), 42 microM) but was much less effective against high K. In single smooth muscle cells loaded with FURA-2, TRIM reduced the increase in fluorescence ratio produced by Tg but had no effect on that produced by high K. The relaxations of Tg-induced tone, and reduction in fluorescence ratio, were obtained in the presence of L-N(G)-nitroarginine and were thus independent of nitric oxide synthase inhibition; further, TRIM had no discernible effect on nitrergic responses. TRIM provides a novel drug for the selective inhibition of CCE and a template for the development of more potent inhibitors.
authors.affiliation: Centre for Cardiovascular Biology & Medicine, School of Biomedical Sciences, King's College London, Hodgkin Building, Guys Campus, London SE1 9RT. alan.gibson@kcl.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Gibson
authors.forename: F
authors.initials: F
authors.lastname: Fernandes
authors.forename: P
authors.initials: P
authors.lastname: Wallace
authors.forename: I
authors.initials: I
authors.lastname: McFadzean
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007093:Imidazoles; D019335:Nitroarginine; C098186:1-(2-trifluoromethylphenyl)imidazole; D019284:Thapsigargin; D019001:Nitric Oxide Synthase; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D011188:Potassium; D002118:Calcium