Role of anti-calcium channel and anti-receptor autoantibodies in autonomic dysfunction in Sjögren's syndrome.
Auto-antibodies cross-reacting with L-type voltage-gated calcium channels (VGCCs) have been described in primary Sjögren's syndrome (pSS), and may mediate the cardiac defects in neonates born to mothers with pSS. L-type VGCCs are also present in autonomically innervated tissues. Therefore, the aim of this project was to investigate a role for anti-VGCC antibodies and antibodies to alpha(1)-adrenoceptors or P(2X)-purinoceptors in the autonomic dysfunction that occurs in pSS. Contraction of the sympathetically innervated vas deferens in response to stimulation of the muscle by an alpha(1)-adrenoceptor agonist (phenylephrine) or a P(2X)-purinoceptor agonist (alpha,beta-methylene ATP) was measured in the absence and presence of 2% serum. Contractions produced by phenylephrine and by alpha,beta-methylene ATP were abolished by nicardipine, demonstrating that they are coupled to calcium influx through L-type VGCCs. Serum from patients with pSS or from healthy controls did not significantly alter the L-type channel-dependent responses of smooth muscle to agonist stimulation. We therefore conclude that pSS serum does not contain autoantibodies that functionally inhibit L-type VGCCs, alpha(1)-adrenoceptors or P(2X)-purinoceptors in smooth muscle and that such autoantibodies cannot explain the autonomic dysfunction in pSS.
Ohlsson
Maria
M
Department of Immunology, Allergy and Arthritis, Flinders University, GPO Box 2100, Adelaide SA 5001, Australia.
Gordon
Tom P
TP
Waterman
Sally A
SA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000276:immunology*; D020746:Calcium Channels, L-Type / Q000032:analysis / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000276:immunology; D009130:Muscle, Smooth / Q000737:chemistry / Q000276:immunology; D010656:Phenylephrine / Q000494:pharmacology; D058913:Purinergic Agonists; D011941:Receptors, Adrenergic / Q000276:immunology; D011983:Receptors, Purinergic / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000150:complications / Q000276:immunology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000276:immunology; D009435:Synaptic Transmission / Q000276:immunology; D014649:Vas Deferens / Q000737:chemistry / Q000276:immunology
D000316:Adrenergic alpha-Agonists; D001323:Autoantibodies; D020746:Calcium Channels, L-Type; D058913:Purinergic Agonists; D011941:Receptors, Adrenergic; D011983:Receptors, Purinergic; D010656:Phenylephrine