Prostacyclin desensitization

Agonist-specific desensitization of prostacyclin-stimulated adenylate cyclase activity has been demonstrated in numerous systems, including human fibroblasts, and platelets in vitro and in vivo ". We have examined the mechanism of desensitization in both human platelets and in cells of the NCB-20 cell line Important and interesting differences have emerged which provide some insights into the events that follow agonist occupation of membrane receptors. 

The problem of in vivo desensitization of platelet responsiveness appears at first sight to limit substantially the potential therapeutic benefit of this family of antiplatelet drugs, but an appreciation of the events involved may yet allow a sensible approach to long-term administration of prostacyclin. Finally, it should be emphasized that the case for prolonged infusions of PGI2 in peripheral vascular disease is not yet firmly established by controlled clinical trials. 

Leigh, P.J. and MacDermot, J. (1985). Desensitization of prostacyclin responsiveness in a neuronal hybrid cell line selective loss of high affinity receptors. Br. J. Pharmacol, 85, 237-247... 

MacDermot, J. (1986). Desensitization of prostacyclin responsiveness in platelets. Apparent differences in the mechanism in vitro or in vivo. Biochem. Pharmacol, 35, 2645-2649... 

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