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Prostacyclin analogues reduce ADP‐ribosylation of the α‐subunit of the regulatory G s ‐protein and diminish adenosine (A 2 ) responsiveness of platelets
Author(s) -
Edwards Robert J.,
MacDermot John,
Wilkins Amanda J.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11199.x
Subject(s) - adenylate kinase , adenosine , cyclase , prostacyclin , platelet , chemistry , gtp' , adp ribosylation , g protein , iloprost , cholera toxin , adenosine diphosphate , heterologous , biochemistry , receptor , endocrinology , medicine , biology , nad+ kinase , enzyme , platelet aggregation , gene
1 Prostacyclin and adenosine activate adenylate cyclase in human platelet membranes and inhibit platelet aggregation. Results are presented which show that prolonged incubation of platelets with iloprost (a stable prostacyclin analogue) results in a reduction in the capacity for adenylate cyclase activation by the adenosine analogue 5′‐(N‐ethyl)‐carboxamidoadenosine (NECA), NaF, guanyl‐5′‐yl imidodiphosphate or GTP. However, iloprost pretreatment resulted in no change in the binding of [ 3 H]‐NECA to platelet membranes. 2 These results contrast with those obtained after pretreatment with 2‐chloroadenosine which revealed no change in NaF or guanyl‐5′‐yl imidodiphosphate sensitivity of adenylate cyclase. Pretreatment with 2‐chloroadenosine resulted in reduced NECA‐dependent adenylate cyclase activation, and loss of [ 3 H]‐NECA binding sites. 3 The heterologous desensitization of adenosine A 2 ‐receptors by iloprost is accompanied by a loss (greater than 80%) of a 45 kDa protein from the plasma membrane, as revealed by [ 32 P]‐ADP‐ribosylation in the presence of cholera toxin. 4 It is proposed that this example of heterologous desensitization is mediated by elimination of G sα , a subunit of the stimulatory guanyl nucleotide‐binding regulatory protein.