title: Mechanisms determining cholinergic neural responses in airways of young and mature rabbits.
abstract: Neural pathways help control airway caliber and responsiveness. Yet little is known of how neural control changes as a function of development. In rabbits, we found electrical field stimulation (EFS) of airway nerves led to more marked contractile responses in 2- vs. 13-week-old animals. This enhanced response to EFS may be due to prejunctional, junctional, and/or postjunctional neural mechanisms. We assessed these mechanisms in airways of 2- and 13-week-old rabbits. The contractile responses to methacholine did not differ in the groups, suggesting postjunctional neural events are not primarily responsible for differing responses to EFS. To address junctional events, acetylcholinesterase (AChE) was measured (spectrophotometry). AChE was elevated in 2-week-olds. However, this should lead to less and not greater responses. Prejunctionally, EFS-induced acetylcholine (ACh) release was assessed by HPLC. Airways of 2-week-old rabbits released significantly more ACh than airways from mature rabbits. Choline acetyltransferase, a marker of cholinergic nerves, was not different between groups, suggesting that more ACh release in young rabbits was not due to increased nerve density. ACh release in the presence of polyarginine increased significantly in both groups, supporting the presence of functional muscarinic autoreceptors (M2) at both ages. Because substance P (SP) increases release of ACh, SP was measured by ELISA. This neuropeptide was significantly elevated in airways of younger rabbits. Nerve growth factor (NGF) increased SP and was also significantly increased in airways from younger rabbits. This work suggests that increases in EFS-induced responsiveness in young rabbits are likely due to prejunctional events with enhanced release of ACh. Increases in NGF and SP early in life may contribute to this increased responsiveness.
authors.affiliation: Division of Pediatric Pulmonary Medicine, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA. larseng@njc.org
authors.forename: Gary L
authors.initials: GL
authors.lastname: Larsen
authors.forename: Joan
authors.initials: J
authors.lastname: Loader
authors.forename: Dee Dee
authors.initials: DD
authors.lastname: Nguyen
authors.forename: Cori
authors.initials: C
authors.lastname: Fratelli
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Giuseppe N
authors.initials: GN
authors.lastname: Colasurdo
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000032:analysis; D000375:Aging / Q000502:physiology*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004558:Electric Stimulation; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009414:Nerve Growth Factors / Q000032:analysis; D011817:Rabbits; D043585:Receptor, Muscarinic M2 / Q000502:physiology; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000032:analysis; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000502:physiology
chemical_list: D016085:Bronchoconstrictor Agents; D009414:Nerve Growth Factors; D043585:Receptor, Muscarinic M2; D011950:Receptors, Cholinergic; D016210:Methacholine Chloride; D013373:Substance P; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine