REVERSIBILITY OF TACHYPHYLAXIS TO C5A IN GUINEA-PIG TISSUES, PERFUSEDHUMAN PLACENTAL LOBULE, AND UMBILICAL ARTERY

The spasmogenic effect of C5a is mediated by histamine and/or eicosano ids. Tachyphylaxis to this effect of C5a occurs rapidly, but the spasm ogenic effects of C5a on a guinea pig lung parenchymal strips, field-s timulated ventricular papillary muscle, and human umbilical artery wer e completely restored by a 1-h period of drug-free rest, whereas that of guinea pig ileum was not. perfusion of the isolated human placental lobule with C5a caused a transient presser response that was largely abolished by indomethacin (5 mu M), indicating mediation by cyclooxyge nase metabolites. This presser response to C5a was also completely res tored following a 1-h rest period. The results show that tissue rest r everses tachyphylaxis to the spasmogenic effects of C5a in tissues whe re the response is mediated by cyclooxygenase metabolites. Where the r esponse is mediated by histamine released by mast cells, restoration d oes not occur, presumably because of the catastrophic nature of mast c ell degranulation. Histamine released in guinea pig papillary muscle b y C5a may be from non-mast-cell sources.