Direct effects of nitric oxide on histamine release from rat enterochromaffin-like cells.
The direct effects of nitric oxide (NO) on enterochromaffin-like (ECL) cells have not yet been demonstrated. In this study we investigated the direct effects of NO donors on rat ECL cells. The NO donor, NOR3 (10 and 100 microM), decreased gastrin-induced histamine release. 100 microM NOR3 increased cGMP levels and reduced gastrin-induced calcium influx. ODQ, an inhibitor of guanylate cyclase, completely blocked NOR3-induced inhibition of histamine release. These results suggest that NO inhibits gastric acid secretion via suppression of gastrin-induced histamine release through a pathway in which NO activates guanylate cyclase, in addition to increasing cGMP levels and reducing gastrin-induced calcium influx. The use of NO as a new type of gastric acid inhibitor that decreases histamine levels in the stomach would be beneficial as increased histamine levels resulting from use of a histamine H2 receptor antagonist or proton pump inhibitor have various effects on tumors and immunological functions.
Shibata
Naozumi
N
Ehime University School of Medicine, Third Department of Internal Medicine, Shitsukawa, Toon-city, Ehime-ken, Japan.
Matsui
Hidetaka
H
Yokota
Tomoyuki
T
Matsuura
Bunzo
B
Maeyama
Kazutaka
K
Onji
Morikazu
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019861:Enterochromaffin-like Cells / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005755:Gastrins / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006632:Histamine / Q000096:biosynthesis; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009574:Nitro Compounds / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D005755:Gastrins; C102260:NOR 4; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D010069:Oxadiazoles; D011725:Pyridines; D011810:Quinoxalines; D009569:Nitric Oxide; D006632:Histamine; C061872:FK 409; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium