Fast deactivation of guinea-pig isolated ileum to C5adesArg: a possible cyclic AMP-dependent mechanism.

The fast component of deactivation of guinea-pig isolated ileum to the spasmogenic action of the complement peptide C5adesArg was further differentiated from the slow component which had been previously analysed (Damerau et al., 1985a, b). Fast deactivation differs from the slow component in the following characteristics: (a) it is unspecific in that it is also induced by C3a, another complement peptide, (b) it depends on the spasmogenic effect of the peptides, and (c) it does not occur at 16 degrees C. In contrast to the slow component, in which the deactivation is thought to be caused by blockade of C5a receptors, fast deactivation seems to be due to a transient increase of intracellular cyclic AMP evoked by C5adesArg and C3a; it is prevented by GDP beta S (5 X 10(-4) M) which blocks activation of adenylate cyclase, and prolonged by agents which sustain cyclic AMP elevations, namely 5 X 10(-4) M theophylline and 5 X 10(-4) M) GTP gamma S.