Distinct tachykinin NK(1) receptor function in primate nucleus tractus solitarius neurons is dysregulated after second-hand tobacco smoke exposure.

Abstract

BACKGROUND AND PURPOSE:

Second-hand tobacco smoke (SHS) exposure in children increases the risk of asthma and sudden infant death syndrome. Epidemiological and experimental data have suggested SHS can alter neuroplasticity in the CNS, associated with substance P. We hypothesized that exposure to SHS in young primates changed the effect of substance P on the plasticity of neurons in the nucleus tractus solitarius (NTS), where airway sensory information is first processed in the CNS.

EXPERIMENTAL APPROACH:

Thirteen-month-old rhesus monkeys were exposed to filtered air (FA, n= 5) or SHS (n= 5) for >6 months from 50 days of their fetal age. Whole-cell patch-clamp recordings were performed on NTS neurons in brainstem slices from these animals to record the intrinsic cell excitability in the absence or presence of the NK(1) receptor antagonist, SR140333 (3 µM).

KEY RESULTS:

Neurons were electrophysiologically classified based on their spiking onset from a hyperpolarized membrane potential into two phenotypes: rapid-onset spiking (RS) and delayed-onset spiking (DS) types. In RS neurons, SR140333 reduced the spiking response, similarly in both FA- and SHS-exposed animals. In DS neurons, SR140333 almost abolished the spiking response in FA-exposed animals, but had no effect in SHS-exposed animals.

CONCLUSIONS AND IMPLICATIONS:

The contribution of NK(1) receptors to cell excitability depended on firing phenotype of primate NTS neurons and was disrupted by SHS exposure, specifically in DS neurons. Our findings reveal a novel NK(1) receptor function in the primate brainstem and support the hypothesis that chronic exposure to SHS in children causes tachykinin-related neuroplastic changes in the CNS.

• Authors: Shin-Ichi Sekizawa, Jesse P Joad, Kent E Pinkerton, Ann C Bonham
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 163 Issue 4 Pg. 782-91 (Jun 2011) ISSN: 1476-5381 [Electronic] England
• PMID: 21323902 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Chemical References

• Neurokinin-1 Receptor Antagonists
• Piperidines
• Quinuclidines
• Receptors, Neurokinin-1
• Tobacco Smoke Pollution
• SR 140333
• Substance P

Topics

• Animals
• Brain Stem (drug effects)
• Female
• Macaca mulatta
• Maternal Exposure (adverse effects)
• Membrane Potentials (drug effects)
• Neurokinin-1 Receptor Antagonists
• Neurons (metabolism)
• Patch-Clamp Techniques (methods)
• Piperidines (pharmacology)
• Pregnancy
• Quinuclidines (pharmacology)
• Receptors, Neurokinin-1 (metabolism)
• Solitary Nucleus (metabolism)
• Substance P (metabolism)
• Tobacco (adverse effects)
• Tobacco Smoke Pollution (adverse effects)