Inhibition of salivary secretion by lipopolysaccharide: possible role of prostaglandins.
Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important in the regulation of the function of different organs during infection. A single dose of lipopolysaccharide (LPS; 5 mg/kg ip) within 6 h increased NOS activity (20%) and prostaglandin E (PGE) content (100%) in submandibular glands (SMG) and blocked stimulated salivary secretion in adult male rats. The administration of an iNOS synthesis inhibitor, aminoguanidine (AG), with LPS decreased NOS activity and PGE content. Furthermore, the administration of meloxicam (MLX), an inhibitor of COX-2, blocked the increase in PGE and the production of NO. The incubation of slices of SMG in the presence of 3-morpholinosydnonimine, a donor of NO, increased the release of PGE highly significantly. The incubation of SMG in the presence of a PGE(1) analog (alprostadil) increased the production of NO. These results indicate that LPS activates NOS, leading to NO release, which activates COX, generating PGEs that act back to further activate NOS, causing further generation of PGEs by activation of COX. Because the alprostadil administration inhibited stimulated salivation, LPS-induced inhibition of salivation appears to be caused by increased PGE production. Diminished salivary secretion produces poor oral health; thus the use of COX-2 inhibitors to counteract the effects of inhibited salivation should be considered.
Lomniczi
A
A
Cátedra de Fisiología, Faculta de Odontología, Universidad de Buenos Aires, 1122, Argentina. lomniczi@yahoo.com
Mohn
C
C
Faletti
A
A
Franchi
A
A
McCann
S M
SM
Rettori
V
V
Elverdin
J C
JC
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001337:Autonomic Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D000077239:Meloxicam; D016210:Methacholine Chloride / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats; D012463:Saliva / Q000378:metabolism*; D013363:Submandibular Gland / Q000187:drug effects* / Q000502:physiology*; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001337:Autonomic Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D007527:Isoenzymes; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D011458:Prostaglandins E; D013843:Thiazines; D013844:Thiazoles; D016210:Methacholine Chloride; D016718:Arachidonic Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000527:Alprostadil; C004479:pimagedine; D000077239:Meloxicam; D009638:Norepinephrine