The objective of this study was to characterize the receptor(s) to
5-HT mediating 5-HTP-induced
diarrhea in mice. The severity of
diarrhea in mice was assessed using an arbitary scoring scale ranging from 0 (normal stools) to 3 (watery
diarrhea). Administration of
5-HTP (1-30 mg/kg i.p.) produced a dose-dependent increase in
diarrhea score (ED50, 1.47 mg/kg i.p.).
5-HTP (10 mg/kg i.p.)-induced
diarrhea was unaffected by
atropine (3 mg/kg i.p.) but was completely abolished by the
aromatic L-amino acid decarboxylase inhibitor
benserazide (10 mg/kg i.p.). Pretreatment (5 min before 5-HTP) with
DAU 6285, a marginally selective
5-HT4 receptor antagonist, significantly inhibited 5-HTP-induced
diarrhea (ID50, 0.58 mg/kg i.p.). Pretreatment (5 min before 5-HTP) with
GR 113808 or
SB 204070, two highly selective
5-HT4 antagonists, significantly inhibited 5-HTP-induced
diarrhea with ID50 estimates of 0.31 and 0.003 mg/kg i.p., respectively. The maximal inhibition produced by
DAU 6285,
GR 113808 and
SB 204070 was 63%, 68% and 36%, respectively. Neither
GR 113808 (1 and 3 mg/kg i.p.) nor
SB 204070 (0.1 and 1 mg/kg i.p.) had any effect on 16,16-dimethyl
prostaglandin E2 (30 micrograms/kg i.p.)-induced
diarrhea in mice.
DAU 6285 significantly inhibited 16,16-dimethyl
prostaglandin E2-induced
diarrhea at the highest dose (3 mg/kg i.p.). Pretreatment (30 min before 5-HTP) with
methysergide (0.1-3 mg/kg i.p.),
metergoline (0.01-0.1 mg/kg i.p.),
ketanserin (0.01-1 mg/kg i.p.),
YM 060 (0.01-0.1 mg/kg i.p.) or
ondansetron (0.01-3 mg/kg i.p.) had no significant effects on 5-HTP-induced
diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)