5-HT activates nitric oxide-generating neurons to stimulate chloride secretion in guinea pig distal colon.
The participation of nitric oxide (NO) in serotonin (5-hydroxytryptamine; 5-HT)-evoked chloride secretion in guinea pig distal colon was examined. Submucosal/mucosal segments were mounted in Ussing flux chambers, and an increase in short-circuit current (Isc) was used as an index of secretion. Addition of 5-HT to the serosal side produced a concentration-dependent (10(-7)-10(-5) M) increase in Isc caused by chloride secretion. NG-nitro-L-arginine (L-NNA) significantly reduced the 5-HT-evoked early (P-1) and late (P-2) responses to 61.1 and 70.6% of control, respectively. Neurally evoked response was also inhibited by L-NNA. The NO donor sodium nitroprusside (SNP, 10(-4) M) increased basal Isc mainly because of chloride secretion. The SNP-evoked response was significantly reduced by tetrodotoxin but was unchanged by atropine or indomethacin. These results suggest that the 5-HT-evoked increase in Isc is associated with an NO-generating mechanism. Atropine significantly reduced the 5-HT (10(-5) M)-evoked P-1 and P-2 responses to 71.8 and 19.7% of control, respectively. Simultaneous application of atropine and L-NNA further decreased the 5-HT-evoked responses more than either drug alone; application of L-NNA and atropine decreased the 5-HT-evoked P-1 and P-2 responses to 68.5 and 39.2% of atropine-treated tissues, respectively. These results suggest that noncholinergic components of P-1 and P-2 responses are 71.8 and 19.7% of control, respectively, and that NO components of P-1 and P-2 responses are 32 and 61%, respectively, of the noncholinergic component of the 5-HT-evoked responses. The results provide evidence that NO may participate as a noncholinergic mediator of 5-HT-evoked chloride secretion in guinea pig distal colon.
Laboratory of Environmental Physiology, Institute for Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
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A
Kuwahara
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H
Kuramoto
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M
Kadowaki
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D002712:Chlorides; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D013779:Tetrodotoxin; D001285:Atropine; D007213:Indomethacin