Ruthenium red and capsaicin induce a neurogenic inflammatory response in the rabbit eye: effects of omega-conotoxin GVIA and tetrodotoxin.
The effects of ruthenium red, an inorganic dye with known capsaicin antagonist properties, was investigated in the rabbit eye. At a dose of 0.24 nmol ruthenium red inhibited the inflammatory effects of capsaicin (1 or 8 nmol). Unexpectedly, when the dye was injected in doses ranging from 0.24 to 7.4 nmol, it caused an inflammatory response with constriction of the pupil (miosis) and a breakdown of the blood-aqueous barrier, leading to a rise intraocular pressure. Tetrodotoxin (30 nmol) inhibited the ruthenium red-induced rise in intraocular pressure but had less effect on the miotic response. The tachykinin antagonist spantide inhibited the miosis but had no effect on the rise in intraocular pressure. Ruthenium red induced an increase in substance P-like immunoreactivity and calcitonin gene-related peptide-like immunoreactivity in the aqueous humor. These levels were positively correlated with the rise in aqueous humor protein concentration. The ruthenium red-induced miosis and, to a less extent, the rise in intraocular pressure were inhibited by the Ca2+ channel-blocking agent omega-conotoxin GVIA (CTX), indicating a partial dependence on an influx of extracellular Ca2+. CTX also attenuated the miotic effect of capsaicin but had no effect on the capsaicin-induced rise in intraocular pressure. It is concluded that, in the rabbit eye, ruthenium red induces a neurogenic inflammatory response besides its capsaicin antagonist effects.
Andersson
S E
SE
Department of Physiology and Medical Biophysics, University of Uppsala, Sweden.
Le Greves
P
P
D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005123:Eye / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D015877:Miosis / Q000139:chemically induced; D015288:Neurokinin A / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011817:Rabbits; D012430:Ruthenium Red / Q000633:toxicity*; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010456:Peptides, Cyclic; D012430:Ruthenium Red; D013373:Substance P; D013779:Tetrodotoxin; D015288:Neurokinin A; C042867:spantide; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin