PMID- 8840130
OWN - NLM
STAT- MEDLINE
DCOM- 19970115
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 308
IP  - 2
DP  - 1996 Jul 18
TI  - Increased defaecation caused by 5-HT4 receptor activation in the mouse.
PG  - 181-6
AB  - The precursor to 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan, (5-HTP, 5-50 
      mg.kg-1) administered subcutaneously (s.c.) to conscious, fed mice caused a dose 
      dependent increase in faecal pellet and fluid output. To avoid provoking watery 
      diarrhoea, all experiments were performed using 5-HTP at 10 mg.kg-1. This dose 
      caused maximal increases in the fluid content (471 +/- 41%) and number of formed 
      faecal pellets defaecated (328 +/- 13% n = 25), 10 and 20 min respectively after 
      administration, when compared to saline-treated mice. In both saline- and 
      5-HTP-treated mice methiothepin, ketanserin, mianserin and granisetron reduced 
      defaecation at high s.c. doses (100 micrograms.kg-1 or 1000 micrograms.kg-1). The 
      5-HT4 receptor antagonists, DAU 6285 
      (endo-6-methoxy-8-methyl-8-azabicyclo[3.2.1]oct-3-yl-2,3-dihydro-2-oxo-1 
      H-benzimidazole-1-carboxylate hydrochloride), SDZ 205-557 
      (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester) and SB 
      204070 ([1-butyl-4-piperidinylmethyl]-8-amino-7-chloro-1,4-benzodioxan -5- 
      carboxylate), had no effects when administered s.c. to saline-treated mice, but 
      dose-dependently inhibited the 5-HTP-evoked responses. Only SB 204070 at 1000 
      micrograms.kg-1 completely inhibited the responses to 5-HTP returning them to 
      normal levels. We conclude that SB 204070 is a potent antagonist for the 
      investigation of 5-HT4 receptor function in both normal and disturbed 
      gastrointestinal activity.
FAU - Banner, S E
AU  - Banner SE
AD  - SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
FAU - Smith, M I
AU  - Smith MI
FAU - Bywater, D
AU  - Bywater D
FAU - Gaster, L M
AU  - Gaster LM
FAU - Sanger, G J
AU  - Sanger GJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Dioxanes)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Antagonists)
RN  - 0 (para-Aminobenzoates)
RN  - 059QF0KO0R (Water)
RN  - 137196-67-9 (2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester)
RN  - 148688-01-1 (SB 204070A)
RN  - 158165-40-3 (Receptors, Serotonin, 5-HT4)
RN  - C1LJO185Q9 (5-Hydroxytryptophan)
RN  - TL2TJE8QTX (4-Aminobenzoic Acid)
SB  - IM
MH  - 4-Aminobenzoic Acid/pharmacology
MH  - 5-Hydroxytryptophan/*pharmacology
MH  - Animals
MH  - Defecation/*drug effects
MH  - Dioxanes/*pharmacology
MH  - Feces/chemistry
MH  - Male
MH  - Mice
MH  - Piperidines/*pharmacology
MH  - Receptors, Serotonin/*drug effects/physiology
MH  - Receptors, Serotonin, 5-HT4
MH  - Serotonin Antagonists/*pharmacology
MH  - Water/analysis
MH  - *para-Aminobenzoates
EDAT- 1996/07/18 00:00
MHDA- 1996/07/18 00:01
CRDT- 1996/07/18 00:00
PHST- 1996/07/18 00:00 [pubmed]
PHST- 1996/07/18 00:01 [medline]
PHST- 1996/07/18 00:00 [entrez]
AID - 0014-2999(96)00296-8 [pii]
AID - 10.1016/0014-2999(96)00296-8 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1996 Jul 18;308(2):181-6. doi: 10.1016/0014-2999(96)00296-8.