Jf. Kachur et al., EICOSANOIDS AND HISTAMINE MEDIATE C5A-INDUCED ELECTROLYTE SECRETION IN GUINEA-PIG ILEAL MUCOSA, Inflammation, 19(6), 1995, pp. 717-725
C5a is a biologically active polypeptide formed during the course of c
omplement activation and is known to possess histamine-releasing and n
eutrophil chemotactic properties. In the present study, we have demons
trated that C5a can regulate electrolyte transport across guinea pig i
leum, and we have investigated its mechanism of action. Segments of il
eum stripped of longitudinal muscle were mounted in Ussing chambers (K
rebs' buffer, 37 degrees C, 95% O-2/5% CO2) for monitoring short-circu
it current (Isc). Serosal application of C5a evoked a transient increa
se in Isc with an EC(50) value of 5.0 nM indicating a potent effect. T
he C5a-induced increase in Isc was abolished by elimination of both Cl
- and HCO3- from the Krebs' solution. Pretreatment with the cyclooxyge
nase inhibitor indomethacin (5 mu M), the neurotoxin tetrodotoxin (0.5
mu M) and the H-1 receptor antagonist pyrilamine (0.5 mu M) reduced t
he effect of C5a, but the muscarinic antagonist atropine (0.5 mu M) wa
s without effect. C5a (100 nM) also evoked the release of histamine (m
easured by radioimmunoassay in the serosal bathing fluid) by 282% of t
he control value. In conclusion. in the guinea pig ileum C5a stimulate
s mucosal anion secretion by releasing histamine and cyclooxygenase pr
oducts of arachidonic acid. The response is also mediated, in part, vi
a non-chloinergic enteric nerves.