Effects of nicotinic receptor blockade on the colonic mucosal response to luminal bile acids in anaesthetized rats.
OBJECTIVE
To test the hypothesis that nicotinic receptor mechanisms mediate the effects of bile acids on the colonic mucosa.


METHODS
The epithelial transport response to 4 mm deoxycholic acid (DCA) was studied in vitro and in vivo, in rat colon. In vitro, epithelial resistance was measured by square pulse analysis, and net membrane current was calculated from the transmucosal potential difference (PD) and resistance. In vivo, we measured PD and net fluid transport.


RESULTS
In vitro, DCA significantly increased membrane current and induced a progressive decrease in epithelial resistance, which in the distal colon eventually resulted in a significant PD reduction. This response was not significantly affected by hexamethonium. In vivo, DCA reduced PD with a significantly larger response in distal colon, but had no consistent effect on net fluid absorption. Nicotinic receptor blockade per se increased net fluid absorption and slightly reduced PD in proximal colon, and inhibited spontaneous net fluid secretion and markedly reduced PD in distal colon. Nicotinic receptor blockade significantly attenuated the bile-acid induced PD response.


CONCLUSIONS
The data do not support the theory that a bile acid-activated secretory reflex exists in rat colon. The reduced PD response after hexamethonium suggests that a mechanism involving nicotinic receptors may potentiate the permeability response to luminal bile acids.
Sun
Ying
Y
Department of Physiology, University of Göteborg, Göteborg, Sweden.
Fihn
Britt-Marie
BM
Jodal
Mats
M
Sjövall
Henrik
H
D000584:Amiloride / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004594:Electrophysiology / Q000379:methods; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018738:Hexamethonium / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D003840:Deoxycholic Acid; D018738:Hexamethonium; D000584:Amiloride