PMID- 23056631 OWN - NLM STAT- MEDLINE DCOM- 20130531 LR - 20231105 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 7 IP - 10 DP - 2012 TI - Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS). PG - e47344 LID - 10.1371/journal.pone.0047344 [doi] LID - e47344 AB - The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS) respond to electric field stimulation (EFS) and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 microM) caused bronchoconstriction in human (4 from 7) and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC). However, this effect was notably smaller in human responder (30 +/- 7.1%) than in guinea pig (79 +/- 5.1%) PCLS. The transient receptor potential (TRP) channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses. FAU - Schleputz, Marco AU - Schleputz M AD - Institute of Pharmacology and Toxicology, RWTH Aachen University, Germany. FAU - Rieg, Annette D AU - Rieg AD FAU - Seehase, Sophie AU - Seehase S FAU - Spillner, Jan AU - Spillner J FAU - Perez-Bouza, Alberto AU - Perez-Bouza A FAU - Braunschweig, Till AU - Braunschweig T FAU - Schroeder, Thomas AU - Schroeder T FAU - Bernau, Marc AU - Bernau M FAU - Lambermont, Verena AU - Lambermont V FAU - Schlumbohm, Christina AU - Schlumbohm C FAU - Sewald, Katherina AU - Sewald K FAU - Autschbach, Rudiger AU - Autschbach R FAU - Braun, Armin AU - Braun A FAU - Kramer, Boris W AU - Kramer BW FAU - Uhlig, Stefan AU - Uhlig S FAU - Martin, Christian AU - Martin C LA - eng PT - Journal Article DEP - 20121009 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Calcium Channel Blockers) RN - 0 (Imidazoles) RN - 11103-72-3 (Ruthenium Red) RN - I61V87164A (1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole) RN - S07O44R1ZM (Capsaicin) SB - IM MH - Animals MH - Bronchoconstriction/*drug effects MH - Calcium Channel Blockers/pharmacology MH - Callithrix MH - Capsaicin/pharmacology MH - Electric Stimulation MH - Guinea Pigs MH - Humans MH - Imidazoles/pharmacology MH - In Vitro Techniques MH - Lung/*drug effects/*metabolism MH - Mice MH - Rats MH - Ruthenium Red/pharmacology MH - Sheep PMC - PMC3467211 COIS- Competing Interests: CS is currently employee at Encepharm GmbH. With respect to the current study CS took responsibility for the supply with NHP material from the German Primate Center Gottingen, a non-commercial institution. There are no competing interests by Encepharm GmbH relating to employment, consultancy, patents, products in development or marketed products. Hence, CS's employment at Encepharm GmbH does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2012/10/12 06:00 MHDA- 2013/06/01 06:00 PMCR- 2012/10/09 CRDT- 2012/10/12 06:00 PHST- 2012/04/20 00:00 [received] PHST- 2012/09/11 00:00 [accepted] PHST- 2012/10/12 06:00 [entrez] PHST- 2012/10/12 06:00 [pubmed] PHST- 2013/06/01 06:00 [medline] PHST- 2012/10/09 00:00 [pmc-release] AID - PONE-D-12-11366 [pii] AID - 10.1371/journal.pone.0047344 [doi] PST - ppublish SO - PLoS One. 2012;7(10):e47344. doi: 10.1371/journal.pone.0047344. Epub 2012 Oct 9.