SUBSTANCE-P AND CAPSAICIN RELEASE PROSTAGLANDIN E-2 FROM RAT INTRAPULMONARY BRONCHI

We hypothesized that substance P and capsaicin would cause the release of prostaglandin E-2 (PGE(2)) from intrapulmonary bronchi isolated fr om Sprague-Dawley rats. Substance P (1 mu M) caused the release of PGE (2), measured with enzyme immunoassay, from the isolated airway segmen ts; PGE2 release was inhibited by the neurokinin (NK)(1)-receptor anta gonist, RP-67580, by inhibition of cyclooxygenase with meclofenamate, and by removal of the epithelium. The release of PGE2 caused by capsai cin (1 mu M) was similar in magnitude to that caused by substance P. T he capsaicin-induced release of PGE2 was inhibited by desensitization of sensory nerves with capsaicin and by RP-67580, meclofenamate, and e pithelial denudation. We conclude that activation of NK1 receptors on epithelium causes release of PGE2, which most likely represents the ul timate mediator of airway smooth muscle relaxation, produced by exogen ous neuropeptides and by activation of the sensory nerve inhibitory sy stem. Epithelial damage, such as that seen in asthmatic airways, would disrupt this protective system in the lungs, which could contribute t o the development of airway disease.