Sodium cromoglycate: evidence of tachykinin antagonist activity in the human skin.
The mechanism of action of the antiasthmatic drug sodium cromoglycate (SCG) is unclear. One possibility is that SCG antagonizes the effects of the tachykinin substance P (SP), an agent known to cause airway edema. However, when SP is inhaled by humans, it has no demonstrable effect on airway function; therefore, the possibility that SCG prevents SP-induced changes in microvascular permeability was examined in human skin in vivo where potent edema-producing effects are seen. SCG (5-500 nmol) caused significant (P < 0.05) dose-dependent inhibition of SP-induced edema (wheal) formation when coadministered by intradermal injection. There was no effect on the nonreceptor-mediated flare response. SCG also significantly (P < 0.05) inhibited the wheal response to the related tachykinin neurokinin B but had no inhibitory effect on the cutaneous responses to histamine and prostaglandin E2. In addition, SCG (0.1-10 mM) caused dose-dependent inhibition of binding of SP labeled with 125I-labeled Bolton-Hunter to a number of tissues known to contain SP binding sites, as assessed by autoradiography. These concentrations were equivalent to the final concentrations of SCG found to inhibit the wheal response in the skin. The possibility that SCG interacted with SP was investigated both by gel filtration and high-performance liquid chromatography. No strong interaction was demonstrated with an 8,000 M excess of SCG under both hydrophobic and hydrophilic conditions. These results raise the possibility that SCG may have tachykinin antagonist properties.
Crossman
D C
DC
Department of Medicine (Cardiology), Hammersmith Hospital, London, United Kingdom.
Dashwood
M R
MR
Taylor
G W
GW
Wellings
R
R
Fuller
R W
RW
D000328:Adult; D001345:Autoradiography; D002199:Capillary Permeability / Q000187:drug effects; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004205:Cromolyn Sodium / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D007271:Injections, Intradermal; D007457:Iodine Radioisotopes; D008297:Male; D015287:Neurokinin B / Q000037:antagonists & inhibitors; D012867:Skin / Q000187:drug effects*; D012882:Skin Tests; D012997:Solvents; D013373:Substance P / Q000037:antagonists & inhibitors; D013388:Succinimides; D015320:Tachykinins / Q000037:antagonists & inhibitors*
D006633:Histamine Antagonists; D007457:Iodine Radioisotopes; D012997:Solvents; D013388:Succinimides; D015320:Tachykinins; D013373:Substance P; C022581:Bolton-Hunter reagent; D015287:Neurokinin B; D015232:Dinoprostone; D004205:Cromolyn Sodium