Loss and recovery of sensitivity of guinea-pig isolated ileum to the spasmogenic action of the complement peptide C5adesArg

Abstract

Deactivation (tachyphylaxis) of the guinea-pig isolated ileum to the spasmogenic action of the complement peptide C5adesArg was analysed. It appeared to consist of 2 components: a fast one, characterized by rapid onset of deactivation and by recovery within 2-3 min (see Damerau et al., 1985b), and a slow component, characterized by progressively increasing loss of sensitivity (until complete deactivation after several minutes) and by recovery within about 80 min. Slow deactivation shows an exponential time course; it is dependent on concentration as well as contact time with C5adesArg and occurs under conditions (incubation in Ca2+-free medium or at 16 degrees C) in which the peptide has no spasmogenic effect. Recovery from slow deactivation follows an exponential time course at 34 degrees C but is blocked at 16 degrees C; on average it reaches about half of the initial sensitivity. The results indicate that the slow deactivation is mainly due to blockade of C5a receptors by the ligand and is independent of the spasmogenic effect of C5adesArg.