Sodium cromoglycate on plasma protein exudation to topically-applied substance P in the tracheal airways of rats or guinea-pigs in vivo.
Sodium cromoglycate (SCG) was examined against substance P(SP)-induced plasma protein exudation in the trachea of anaesthetized rats and guinea-pigs in vivo to determine whether SCG is a tachykinin receptor antagonist in the airways. A segment of trachea was prepared in situ for continuous perfusion with normal saline. Plasma-derived protein in the perfusion fluid (airway lumen) was increased after topical application of SP (1 microM, 5 min contact). In rats, the SP response was not attenuated by iv SCG but was inhibited (29%) by topical SCG under certain experimental conditions and using a high concentration of SCG (500 microM, 5 min contact, 30 min before SP and with SP). The NK(1)receptor antagonist, RP 67 580 (67 microM) abolished the SP response in rats. Sodium cromoglycate did not inhibit the SP response in guinea-pigs (same protocol as in rats). Thus, SCG attenuates plasma protein exudation (and presumably microvascular leak) induced by SP in rat tracheal airways but, if SCG is a tachykinin receptor (NK(1)) antagonist, it not only lacks potency but is species-selective, i.e. more effective in rats than in guinea-pigs.
O'Donnell
S R
SR
Pulmonary Pharmacology Group, Department of Physiology and Pharmacology, The University of Queensland, Brisbane, Queensland 4072, Australia. odonnell@plpk+uq.edu.au
Coulson
F R
FR
Bigg
C S
CS
D000287:Administration, Topical; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism*; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D054833:Isoindoles; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D013373:Substance P; D014132:Trachea / Q000187:drug effects*
D018927:Anti-Asthmatic Agents; D001798:Blood Proteins; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D018039:Receptors, Tachykinin; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D004205:Cromolyn Sodium