Comparison of distal lung innervation in human and guinea pig precision-cut lung slices (PCLS)

Introduction: PCLS from human tissue are well suited to study peripheral airway responses. Since autonomic nerves are involved in airway control and in several diseases including allergic airway hyperreactivity, we characterized distal lung innervation in guinea pigs (GP) with respect to bronchoconstriction (BC) and compared the results to those with human PCLS. Methods: PCLS were prepared from GP or human lung tissue. Neural activation was triggered by electric field stimulation (EFS) or capsaicin addition. Cholinergic innervation was verified by atropine. Capsaicin was used to show excitatory non-adrenergic non-cholinergic (eNANC) nerves. Application of Ruthenium red or SKF96365 confirmed transient receptor potential (TRP) channel contributions upon eNANC activation. Results: GP and human PCLS were both sensitive to EFS and airways contracted to 39±26% of the initial airway area (%-IAA) and 42±30%-IAA, respectively. Frequency response curves were also similar. For both species, EFS-induced BC was decreased after the addition of atropine. Capsaicin contracted GP and human airways to 18±15%-IAA and to 62±6%-IAA, respectively. Capsaicin-triggered BC was inhibited in GP by Ruthenium red and SKF96365. Both inhibitors also reduced EFS-induced BC in PCLS from GP. Conclusion: Both species contain atropine sensitive cholinergic and capsaicin sensitive eNANC nerves. In addition, GP PCLS were sensitive to TRP channel inhibitors allowing the study of their contribution in the pathogenesis of lung diseases. In conclusion, GP PCLS represent a useful model to study pharmacological aspects of lung innervation and resemble the human distal lung innervation.