ah-23848 and Fever

This study was carried out to investigate whether the pulmonary C-fiber hypersensitivity induced by hyperthermia is altered by prostaglandin E(2) (PGE(2)). Single-unit afferent activities of pulmonary C-fibers were recorded in anesthetized, artificially ventilated rats when the intrathoracic temperature (T(it)) was maintained at normal (N; approximately 36 degrees C) and hyperthermia levels (H; approximately 41 degrees C) by perfusion of heated saline into the thoracic chamber for 3min. After approximately 20min of recovery, the fiber activities were recorded again during infusion of PGE(2) at both N and H levels of T(it). Our study showed: (1) The baseline fiber activity and responses to lung inflation, right-atrial injection of capsaicin and adenosine were all increased by increasing T(it) from N to H, and these hyperthermia-induced increases in sensitivities were also significantly augmented by PGE(2). (2) These enhanced sensitivities induced by PGE(2) were abolished by pretreatment with AH6809 and AH23848, selective antagonists of EP(2) and EP(4) prostanoid receptors, respectively. In conclusion, the hyperthermia-induced hypersensitivity of vagal pulmonary C-fibers is potentiated by PGE(2), and this effect is mediated through activation of EP(2) and EP(4) prostanoid receptors.

Topics: Anesthesia; Animals; Biphenyl Compounds; Body Temperature; Dinoprostone; Fever; In Vitro Techniques; Infusions, Intravenous; Lung; Male; Nerve Fibers, Unmyelinated; Neurons, Afferent; Pneumonia; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP2 Subtype; Receptors, Prostaglandin E, EP4 Subtype; Respiration, Artificial; Xanthones