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. Author manuscript; available in PMC: 2018 Aug 5.
Published in final edited form as: Nat Neurosci. 2018 Feb 5;21(3):324–328. doi: 10.1038/s41593-018-0074-8

Figure 2. MrgprC11+ jugular sensory neurons mediate cholinergic bronchoconstriction.

Figure 2

(a) Diagram showing the neural pathway mediating parasympathetic cholinergic bronchoconstriction. (b) Retro-orbital I.V. injection of Bam8-22 induced bronchoconstriction in WT, but not Mrgpr-clusterΔ−/− mice. Reversed Bam8-22 peptide did not induce bronchoconstriction. Subcutaneous and intrathecal administration of Bam8-22 to activate the peripheral and central terminals of MrgprC11+ DRG sensory neurons, respectively, did not induce bronchoconstriction, consistent with the fact that MrgprC11+ DRG sensory neurons do not innervate the airway. (WT i.v., n=8; KO iv, n=7; WT reversed, n=6; WT subQ, n=6; WT i.t. n=6; WT i.v. Baseline vs Bam8-22, p=5.36E-05). (c) Bam8-22-induced bronchoconstriction was blocked by cholinergic blocker ipratropium bromide. (Naïve, n=6; Ipra, n=5; p=0.00085). (d) Bam8-22-induced bronchoconstriction was blocked by vagotomy. (Sham, n=7; Vagotomy, n=7; p=0.004). (e) Representative trace of airway smooth muscle contraction in response to electrical field stimulation and Bam8-22. Electrical field stimulation (12V, 8HZ, 0.5ms, 10s) induced robust contraction of mouse trachea, but Bam8-22 (10uM) did not. Arrow indicates the addition of Bam8-22. Black dots indicate the electrical field stimulation. The results were repeated in three animals. Cholinergic contractile response of mouse trachea to electrical field stimulation (12V, 8HZ, 0.5ms, 10s) was not changed by the addition of Bam8-22 (28.3±1.80 vs 30.2±2.75 % of Maximum contraction). (f) Retro-orbital I.V. injection of Bam8-22 (400 μl, 20 mg/ml) induced bronchoconstriction in guinea pigs. (PBS, n=5; Bam8-22, n=6; PBS vs Bam8-22, p=0.018). *p< 0.05, ***p< 0.005, two-tailed unpaired Student’s t test. Data are reported as mean ± s.e.m.