Acute effects of high-dose intragastric nicotine on mucosal defense mechanisms: an analysis of nicotine, prostaglandin E2, phospholipase A2, and phospholipids.
Peptic ulcer disease is overrepresented among smokers; they also heal slowly and relapse frequently. Data are accumulating that smoking is detrimental to gastroduodenal mucosal cytoprotection. This study was designed to assess acute effects of high-dose intragastric nicotine, as it has been shown that nicotine is accumulated in gastric juice when smoking. Seven healthy smokers were given nicotine base (6 mg) as tablets, which yielded very high intragastric concentrations and plasma levels comparable to those seen when smoking. In addition to nicotine analysis, concentration levels of prostaglandin E2 (PGE2), phospholipase A2 (PLA2), and phospholipid classes were measured before and after nicotine administration. Nicotine inhibited PGE2 levels by 27-81%, whereas PLA2 and total phospholipids were unaffected. Lysolecithin, a degradation product of the main constituent of gastric surfactant, ie, phosphatidylcholine, tended to increase, but this was not reflected in intragastric phosphatidylcholine levels. In conclusion, nicotine acutely inhibits PGE2 and may thus impair mucosal cytoprotection. The present findings do not imply a central role of surface-active phospholipids with respect to nicotine and gastric cytoprotection, but the chronic effects of nicotine remain to be investigated.
Lindell
G
G
Department of Surgery, Lund University, Sweden.
Bukhave
K
K
Lilja
I
I
Madsen
J R
JR
Graffner
H
H
D000328:Adult; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005745:Gastric Acidity Determination; D005750:Gastric Juice / Q000737:chemistry / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D010741:Phospholipases A / Q000187:drug effects* / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism; D013270:Stomach; D013607:Tablets
D018722:Nicotinic Agonists; D010743:Phospholipids; D013607:Tablets; D009538:Nicotine; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone