A. Bozkurt et al., Cefaclor, a cephalosporin antibiotic, delays gastric emptying rate by a CCK-A receptor-mediated mechanism in the rat, BR J PHARM, 131(3), 2000, pp. 399-404
1 Studies in vitro suggest that cephalosporin antibiotics release the gut h
ormone cholecystokinin. Cholecystokinin is known to inhibit gastric emptyin
g. Here we examine the effects of cefaclor on gastric emptying and intestin
al motility.
2 Male Sprague-Dawley rats were fitted with gastric cannulas. Following a 3
-week recovery, the rate of gastric emptying of saline, peptone (4.5%) or c
efaclor was determined after instillation into the gastric cannula, while i
ntestinal transit was measured by using the propagation of arabic gum + cha
rcoal mixture given intraduodenally.
3 Gastric emptying of saline was significantly delayed by the addition of c
efaclor (3, 10, 30 or 100 mM). The CCK-A antagonist SR-27897B (1 mg kg(-1),
i.p.) reversed the delay induced by 10 mM cefaclor, whereas the CCK-B anta
gonist CI-988 (1 mg kg(-1), i.p.) had no significant effect. In capsaicin-t
reated rats, 10 mM cefaclor emptied more rapidly than in vehicle-treated an
imals.
4 Thirty-minute intestinal transit was increased at 30 and 100 mM of cefacl
or, while the gastric acid secretion following cefaclor instillation was no
different than the group which received saline.
5 The cephalosporin antibiotic cefaclor appears to be a potent stimulant of
CCK release from gut endocrine cells, resembling the effects of peptone. C
efaclor delays gastric emptying via capsaicin-sensitive afferent pathways,
which involve CCK-A receptor interaction.