THE INFLUENCE OF POSTMORTEM CONDITIONS ON CONTRACTILE AND RELAXANT RESPONSIVENESS OF GUINEA-PIG ISOLATED TRACHEAL SMOOTH-MUSCLE

Responsiveness to various contractile and relaxant agonists was assess ed in tracheal preparations from guinea-pigs that had been incubated i n situ at 4-37 degrees C for 0-168 h post-mortem The potencies of hist amine and acetylcholine were increased up to 168 h at 4 degrees C post -mortem and up to 24 h post-mortem at 22 degrees C. Histamine potency also increased with increasing post-mortem time at 37 degrees C. After 48 h at 22 degrees C and 8 h at 37 degrees C, responses to all spasmo gens were abolished. Increases in histamine and acetylcholine potencie s were similarly observed in tracheal tissue that had been removed at death and then incubated at 4 degrees C in oxygenated Krebs-bicarbonat e solution for 0-168 h. The increased potency of these drugs may be ex plained by epithelial damage and/or loss of an epithelium-derived inhi bitory factor (EpDIF). Both basal and spasmogen-stimulated increases i n intracellular phosphoinositides fell with increasing time and ambien t temperature post-mortem, despite the fact that contraction in respon se to these agonists could still be evoked. This suggests the selectiv e failure of this signal transduction pathway and the maintenance of r esponsiveness via other mechanisms. The potencies and maximum effects of relaxant agonists remained unaltered in tracheal tissue with increa sing time post-mortem, suggesting little change in the function of the appropriate receptor-signal transduction processes. This study has th erefore demonstrated that at 4 degrees C, contractile and relaxant res ponses were preserved for up to 168 h post-mortem, although the modula tory influence of the epithelium on histamine and acetylcholine respon ses was rapidly lost.