Cholinergic autoantibodies from primary Sjögren's syndrome modulate submandibular gland Na+/K+-ATPase activity via prostaglandin E2 and cyclic AMP.
We demonstrate that patients with primary Sjögren's syndrome (pSS) produce functional IgG autoantibodies that interact with the glandular M(3) muscarinic acetylcholine receptors (mAChRs). These autoantibodies act as a partial muscarinic agonist, increasing prostaglandin E(2) (PGE(2)) and cyclic AMP production through modifying Na(+)/K(+)-ATPase activity, but also interfere with the secretory effect of the parasympathetic neurotransmitter. The IgG from patients with pSS has two effects on the submandibular gland. On the one hand, it may act as an inducer of the proinflammatory molecule (PGE(2)) that, in turn, inhibits Na(+)/K(+)-ATPase activity. On the other hand, it plays a role in the pathogenesis of dry mouth, abolishing the Na(+)/K(+)-ATPase inhibition and the net K(+) efflux stimulation of the salivary gland in response to the authentic agonist pilocarpine, decreasing salivary fluid production.
Passafaro
Daniela
D
Pharmacology Unit, School of Dentistry, Buenos Aires University, Buenos Aires, Argentina.
Reina
Silvia
S
Sterin-Borda
Leonor
L
Borda
Enri
E
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D007638:Keratoconjunctivitis Sicca / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000276:immunology* / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3 / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013363:Submandibular Gland / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D014331:Tropicamide / Q000494:pharmacology; D014987:Xerostomia / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018836:Inflammation Mediators; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D043587:Receptor, Muscarinic M3; D010862:Pilocarpine; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D015232:Dinoprostone; D014331:Tropicamide; D011188:Potassium