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Published ahead of print on December 14, 2006, doi:10.1165/rcmb.2006-0256OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 36, pp. 541-551, 2007
© 2007 American Thoracic Society
DOI: 10.1165/rcmb.2006-0256OC

Sensory Receptors in the Visceral Pleura

Neurochemical Coding and Live Staining in Whole Mounts

Isabel Pintelon, Inge Brouns, Ian De Proost, Frans Van Meir, Jean-Pierre Timmermans and Dirk Adriaensen

Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium

Correspondence and requests for reprints should be addressed to Dirk Adriaensen, Ph.D., Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Groenenborgerlaan 171, BE-2020 Antwerp, Belgium. E-mail: dirk.adriaensen{at}ua.ac.be

Today, diagnosis and treatment of chest pain related to pathologic changes in the visceral pleura are often difficult. Data in the literature on the sensory innervation of the visceral pleura are sparse. The present study aimed at identifying sensory end-organs in the visceral pleura, and at obtaining more information about neurochemical coding. The immunocytochemcial data are mainly based on whole mounts of the visceral pleura of control and vagally denervated rats. It was shown that innervation of the rat visceral pleura is characterized by nerve bundles that enter in the hilus region and gradually split into slender bundles with a few nerve fibers. Separate nerve fibers regularly give rise to characteristic laminar terminals. Because of their unique association with the elastic fibers of the visceral pleura, we decided to refer to them as "visceral pleura receptors" (VPRs). Cryostat sections of rat lungs confirmed a predominant location on mediastinal and interlobar lung surfaces. VPRs can specifically be visualized by protein gene product 9.5 immunostaining, and were shown to express vesicular glutamate transporters, calbindin D28K, Na+/K+-ATPase, and P2X3 ATP-receptors. The sensory nerve fibers giving rise to VPRs appeared to be myelinated and to have a spinal origin. Because several of the investigated proteins have been reported as markers for sensory terminals in other organs, the present study revealed that VPRs display the neurochemical characteristics of mechanosensory and/or nociceptive terminals. The development of a live staining method, using AM1-43, showed that VPRs can be visualized in living tissue, offering an interesting model for future physiologic studies.

Key Words: lung • P2X3 ATP-receptors • vesicular glutamate transporters • visceral pleura • receptors


CLINICAL RELEVANCE

Visceral pleura receptors (VPRs) likely mediate the sensory transduction of mechanical and/or nociceptive stimuli. VPRs are potentially involved in the hitherto unknown mechanisms of pain sensation and (reflex) dyspnea regularly described to result from pleural disease.

 






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