Interaction of TRPV1 and EP3 Receptor in Cough and Bronchopulmonary C-Neural Activities

Abstract

Prostaglandin E2 (PGE2)-induced coughs in vivo and vagal nerve depolarization in vitro are inhibited by systemic and local administration of TRPV1 (JNJ 17203212) and prostaglandin EP3 receptor antagonists (L-798106) respectively. These results indicate an interaction of TRPV1 and EP3 receptor in cough responses to PGE2 likely through the vagal sensory nerve. This study aimed to determine whether 1) inhalation of aerosolized JNJ 17203212 and L-798106 affected cough responses to citric acid (CA to mainly stimulate TRPV1) and PGE2; 2) TRPV1 and EP3 receptor morphologically co-expressed and electrophysiologically functioned in the individual of vagal pulmonary C-neurons (cell bodies of bronchopulmonary C-fibers in the nodose/jugular ganglia); and 3) the interaction of the two receptors occurred in these neurons. To this end, aerosolized CA or PGE2 was inhaled by unanesthetized guinea pigs pretreated without or with JNJ 17203212 or L-798106 given in aerosol. Immunofluorescence was applied to identify the expression of the two receptors in vagal pulmonary C-neurons (retrogradely traced by DiI). Whole-cell patch clamp approach was used to detect capsaicin (CAP)- and PGE2-induced currents in the same neurons and determine the effects of the TRPV1 and EP3 receptor antagonists on the currents. We found that PGE2-evoked cough was attenuated by JNJ 17203212 or L-798106 and CA-evoked cough greatly suppressed only by JNJ 17203212. EP3-labeled neurons always co-expressed TRPV1 with a cell size < 20 µm and occupied 1/4 of vagal pulmonary C-neurons. Both CAP- and PGE2-induced currents could be recorded in the individuals of some vagal pulmonary C-neurons. The former was largely inhibited only by JNJ 17203212, while the latter was suppressed by JNJ 17203212 or L-798106. The similarity of the interaction in cough and vagal pulmonary C-neural activity suggests that a subgroup of vagal pulmonary C-neurons co-expressing TRPV1 and EP3 receptor is, at least in part, responsible for the interaction of the two receptors in the cough response to PGE2.

Neurogenic substance P—influences on action potential production in afferent neurons of the kidney?

“…The described technique for staining neurons has been used by us for many years and was described in several publications [ 13 , 15 , 16 , 36 , 37 , 51 ]. It has also been successfully used by others [ 18 , 22 , 24 , 25 ]. Using this approach, after renal denervation, it is no longer possible to detect labelled neurons in the dorsal root ganglia Th12 to L2, where the first neurons of renal afferent nerve fibers can be found .…”