Involvement of serotonin and calcium channels in the intestinal fluid secretion evoked by bile salt and cholera toxin.
1. The enteric nervous system (ENS) is activated when exposing the intestinal mucosa to cholera toxin or certain bile salts. Cholera toxin stimulates ENS, at least in part, by the release of 5-hydroxytryptamine (5-HT) from the enterochromaffin cells. Calcium channel blockers of the L-type markedly attenuate the fluid secretion and the luminal release of 5-HT caused by cholera toxin. 2. The objective of the present study was to elucidate if sodium deoxycholate activated ENS in a similar manner as cholera toxin. Furthermore, the effect of several calcium channel blockers was tested on the fluid secretion caused by cholera toxin or bile salt. 3. Sodium deoxycholate (4 mM) caused a release of 5-HT into the intestinal lumen, which was inhibited by calcium channel blockade. Granisetron, a 5-HT3 receptor blocker, partly inhibited the fluid secretion caused by bile salt. 4. The effects of nifedipine, felodipine, R-felodipine, H186/86 (t-butyl analogue of felodipine) on the fluid secretion caused by cholera toxin or sodium deoxycholate were studied. Both secretory states were markedly attenuated in a dose dependent manner by all calcium channel blockers tested regardless of their effects on arterial pressure. 5. It is concluded that both cholera toxin and bile salt activate ENS, at least in part, via a release of 5-HT from the enterochromaffin cells. The antisecretory effect calcium channel blockers is partly explained by an inhibition of this release of 5-HT.
Peregrin
A T
AT
Department of Physiology, Göteborg University, Gothenburg, Sweden.
Ahlman
H
H
Jodal
M
M
Lundgren
O
O
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002772:Cholera Toxin / Q000494:pharmacology*; D015736:Felodipine / Q000494:pharmacology; D017829:Granisetron / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*
D001647:Bile Acids and Salts; D015220:Calcium Channels; D002772:Cholera Toxin; D015736:Felodipine; D017829:Granisetron; D009543:Nifedipine; D012701:Serotonin