Prenatal Nicotinic Exposure (PNE) Promotes Pulmonary IL‐1β and 5‐HT and Gene/Protein Expression of IL1R1, NK1R, ADRA1, and TRPV1 in N/J ganglia Neurons via Acting on α7nAChRs in Rat Pups

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We have shown that PNE sensitizes bronchopulmonary C‐fibers (PCFs) in rat pups. Here we asked if PNE was able to increase the pulmonary mediators known to sensitize/active PCFs, and their corresponding receptors expressed in nodose/jugular (N/J) ganglion neurons in P11‐14 pups. If so, we further asked if the evoked changes depended on nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR. We compared IL‐1β, substance P (SP), serotonin (5‐HT), and adenosine (AD) in BALF and IL‐1 type I receptor (IL1R1), NK1R, TRPV1, and adenosine A1 receptor (ADRA1) in the N/J ganglia in P11‐14 rat pups prenatally exposed to saline (Ctrl) and PNE alone or coupled with mecamylamine (MM), a non‐selective blockade of nAChRs and methyllycaconitine (MLA), a selective blockade of α7nAChR. We found that PNE significantly augmented IL‐1β and 5‐HT but not SP and AD in BALF and gene and protein expressions of IL1R1, NK1R, TRPV1, and ADRA1 in the N/J ganglia. Both MM and MLA abolished the responses of IL‐1β and 5‐HT in BALF. MM eliminated the gene and protein responses of N/J ganglion TRPV1, NK1R, IL1R1, and ADRA1 to PNE except little effect on IL1R1 gene, while MLA eliminated all of the gene responses. Our data suggest that PNE is able to elevate IL1R1, NK1R, ADRA1, and TRPV1 in the N/J ganglia, which, along with increased IL‐1β and 5‐HT releases in the lungs, likely contributes to sensitize/activate PCFs. These PNE‐induced modulations are greatly dependent on the activation of α7nAChRs (Supported by HL‐107462).