Examination of the possible role of prostanoids on responses of guinea-pig isolated, perfused trachea (IPT) to luminally-applied isotonic osmolyte solutions.
Fedan-JS; Peppers-JA; Johnston-RA
FASEB J 2001 Mar; 15(5):A862
Exposure of the mucosa of the IPT to modified Krebs-Henseleit solution (MKHS) containing elevated osmolarity [added NaCl or D-mannitol (DM)] results in relaxation of methacholine (MCh)-contracted airway smooth muscle that is mediated by epithelium-derived relaxing factor (EpDRF). The stimulus to EpDRF release in response to hypertonic challenge could involve cell shrinkage or activation of an osmotic sensor. To distinguish between these possibilities, IPT were contracted with serosally-applied MCh (3 X 10*7 M) while perfusing with MKHS. At the plateau of the contraction the perfusion solution was changed rapidly to solutions of NaCl or D-M that were isotonic with MKHS. This procedure causes cell shrinkage in other cell types. It was observed that a variety of responses to isotonic NaCl or D-M were elicited, including modest relaxation, no effect, or contraction. That is, the typical large relaxation responses to these agents when they are used to raise the tonicity of MKHS solution were not seen. To explore the possibility that the responses to isotonic NaCl or D-M were complex and varying due to the release of prostanoids, responses to mucosal isotonic NaCl or D-M solutions were obtained in the presence of indomethacin (3 X 10^-6 M; mucosal and serosal) to block cyclooxygenase. Indomethacin had no effect on responses to perfusion with isotonic NaCl or D-M. These findings suggest that EpDRF release in response to hypertonicity does not result fomr cell shrinkage per se and that the various responses of the IPT to mucosally-applied isotonic NaCl or D-M do not involve prostanoids.
Exposure-levels; Methacholines; In-vitro-study; Cell-cultures; Cell-function; Cellular-function; Cellular-reactions
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