Am. J. Respir. Cell Mol. Biol., Volume 23, Number 1, July, 2000 52-61

Intraepithelial Vagal Sensory Nerve Terminals in Rat Pulmonary Neuroepithelial Bodies Express P2X₃ Receptors

Inge Brouns, Dirk Adriaensen, Geoff Burnstock, and Jean-Pierre Timmermans

Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium; and Autonomic Neuroscience Institute, Royal Free Hospital School of Medicine, London, United Kingdom

The neurotransmitters/modulators involved in the interaction between pulmonary neuroepithelial bodies (NEBs) and the vagal sensory component of their innervation have not yet been elucidated. Because P2X₃ purinoreceptors are known to be strongly expressed in peripheral sensory neurons, the aim of the present study was to examine the localization of nerve endings expressing P2X₃ purinoreceptors in the rat lung in general and those contacting pulmonary NEBs in particular. Most striking were intraepithelial arborizations of P2X₃ purinoceptor-immunoreactive (IR) nerve terminals, which in all cases appeared to ramify between calcitonin gene-related peptide (CGRP)- or calbindin D28k (CB)-labeled NEB cells. However, not all NEBs received nerve endings expressing P2X₃ receptors. Using CGRP and CB staining as markers for two different sensory components of the innervation of NEBs, it was revealed that P2X₃ receptor and CB immunoreactivity were colocalized, whereas CGRP-IR fibers clearly formed a different population. The disappearance of characteristic P2X₃ receptor-positive nerve fibers in contact with NEBs after infranodosal vagal crush and colocalization of tracer and P2X₃ receptor immunoreactivity in vagal nodose neuronal cell bodies in retrograde tracing experiments further supports our hypothesis that the P2X₃ receptor-IR nerve fibers contacting NEBs have their origin in the vagal sensory nodose ganglia. Combination of quinacrine accumulation in NEBs, suggestive of the presence of high concentrations of adenosine triphosphate (ATP) in their secretory vesicles, and P2X₃ receptor staining showed that the branching intraepithelial P2X₃ receptor-IR nerve terminals in rat lungs were exclusively associated with quinacrine-stained NEBs. We conclude that ATP might act as a neurotransmitter/neuromodulator in the vagal sensory innervation of NEBs via a P2X₃ receptor-mediated pathway. Further studies are necessary to determine whether the P2X₃ receptor-expressing neurons, specifically innervating NEBs in the rat lung, belong to a population of P2X₃ receptor-IR nociceptive vagal nodose neurons.

This article has been cited by other articles:

				I. Pintelon, I. Brouns, I. De Proost, F. Van Meir, J.-P. Timmermans, and D. Adriaensen Sensory Receptors in the Visceral Pleura: Neurochemical Coding and Live Staining in Whole Mounts Am. J. Respir. Cell Mol. Biol., May 1, 2007; 36(5): 541 - 551. [Abstract] [Full Text] [PDF]

				G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]

				D. Adriaensen, I. Brouns, I. Pintelon, I. De Proost, and J.-P. Timmermans Evidence for a role of neuroepithelial bodies as complex airway sensors: comparison with smooth muscle-associated airway receptors J Appl Physiol, September 1, 2006; 101(3): 960 - 970. [Abstract] [Full Text] [PDF]

				G. Burnstock Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol. Rev., March 1, 2006; 58(1): 58 - 86. [Abstract] [Full Text] [PDF]

				J. Pan, I. Copland, M. Post, H. Yeger, and E. Cutz Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L185 - L193. [Abstract] [Full Text] [PDF]

				K. Dang, K. Bielfeldt, K. Lamb, and G. F. Gebhart Gastric Ulcers Evoke Hyperexcitability and Enhance P2X Receptor Function in Rat Gastric Sensory Neurons J Neurophysiol, June 1, 2005; 93(6): 3112 - 3119. [Abstract] [Full Text] [PDF]

				J. Van Genechten, I. Brouns, G. Burnstock, J.-P. Timmermans, and D. Adriaensen Quantification of Neuroepithelial Bodies and Their Innervation in Fawn-Hooded and Wistar Rat Lungs Am. J. Respir. Cell Mol. Biol., January 1, 2004; 30(1): 20 - 30. [Abstract] [Full Text] [PDF]

				W. Rong, A. V. Gourine, D. A. Cockayne, Z. Xiang, A. P. D. W. Ford, K. M. Spyer, and G. Burnstock Pivotal Role of Nucleotide P2X2 Receptor Subunit of the ATP-Gated Ion Channel Mediating Ventilatory Responses to Hypoxia J. Neurosci., December 10, 2003; 23(36): 11315 - 11321. [Abstract] [Full Text] [PDF]

				X. W. Fu, C. A. Nurse, S. M. Farragher, and E. Cutz Expression of functional nicotinic acetylcholine receptors in neuroepithelial bodies of neonatal hamster lung Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1203 - L1212. [Abstract] [Full Text] [PDF]

				P. P. Bertrand ATP and Sensory Transduction in the Enteric Nervous System Neuroscientist, August 1, 2003; 9(4): 243 - 260. [Abstract] [PDF]

				W. L. Neuhuber Lung Sensors: Complex Functions Require Complex Structures Am. J. Respir. Cell Mol. Biol., March 1, 2003; 28(3): 265 - 266. [Full Text] [PDF]

				I. Brouns, J. Van Genechten, H. Hayashi, M. Gajda, T. Gomi, G. Burnstock, J.-P. Timmermans, and D. Adriaensen Dual Sensory Innervation of Pulmonary Neuroepithelial Bodies Am. J. Respir. Cell Mol. Biol., March 1, 2003; 28(3): 275 - 285. [Abstract] [Full Text] [PDF]

				I. Brouns, L. Van Nassauw, J. Van Genechten, M. Majewski, D. W. Scheuermann, J.-P. Timmermans, and D. Adriaensen Triple Immunofluorescence Staining with Antibodies Raised in the Same Species to Study the Complex Innervation Pattern of Intrapulmonary Chemoreceptors J. Histochem. Cytochem., April 1, 2002; 50(4): 575 - 582. [Abstract] [Full Text] [PDF]

				B. A. Chizh and P. Illes P2X Receptors and Nociception Pharmacol. Rev., December 1, 2001; 53(4): 553 - 568. [Abstract] [Full Text] [PDF]