OP0031 Development of a novel epitope-based diagnostic assay for systemic sclerosis

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Pharmacological Characterizazion of Muscarinic Receptor Subtypes in Rabbit Isolated Tissue Preparation

1. The affinity of some muscarinic antagonists for muscarinic receptors was determined in functional isolated tissue studies in order to compare the muscarinic receptor subtypes in the rabbit.2. Our attention was specially focused on the question of whether the muscarinic receptors mediating vasodilatation in the aorta resemble or not the ones present on the jejunum of the gastrointestinal tract.3. Isolated aorta, jejunum, stimulated left atrium and vas deferens preparations of rabbit were investigated with the following muscarinic antagonists: atropine, pirenzepine, methoctramine (N,N'-bis[6-(2-methoxybenzyl)amino hexyl]-1, 8-octane-diamine tetrahydrochloride) and 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide).4 .The results demonstrate that the receptors on aorta are unlike those on the other rabbit tissues: pirenzepine pA2 was 6.4 on aorta but 8.1 on vas deferens; methoctramine pA2 was 5.9 on aorta but 7.1 on heart; 4-DAMP pA2 was 8.7 on aorta and 8.0 on jejunum. This raises the question: what subtype might be involved

Stimulatory autoantibodies to the PDGF receptor: a link to fibrosis in scleroderma and a pathway for novel therapeutic targets.

Systemic sclerosis (scleroderma) is a complex disease characterized by excessive deposition of collagen and abnormalities of blood vessels. In addition, activation of the immune system is a central feature of scleroderma as shown by mononuclear cell infiltration of the skin, autoantibody production and release of inflammatory cytokines. The pathogenesis of the disease is poorly understood and the molecular events underlying the main clinical features are not known. The detection of agonistic autoantibodies targeting PDGF receptor in serum of patients with scleroderma may indicate a novel link between phenotypic features of the disease and a specific signalling pathway. Agonistic PDGF receptor antibodies induce in vitro the scleroderma phenotype in normal human fibroblasts and, thus, link autoimmunity to fibrosis. These findings pave the way to novel therapeutic strategies

Spectral analysis of intercycle heart fluctuations in the diethyl ether-anaesthetized or pithed rat treated with prazosin, dl-propranolol, endothelin-1, \u3b1-r atriopeptin and ACE-inhibitors

NRC publication: Ye