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Islet-activating protein impairs α 2-adrenoceptor-mediated inhibitory regulation of human platelet adenylate cyclase

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Summary

Human platelet adenylate cyclase is stimulated by prostaglandin E1 (PGE1) and inhibited by adrenaline acting via α2-adrenoceptors. Both hormonal factors increase GTP hydrolysis in platelet membranes by stimulation of a high affinity GTPase. The influence of the Bordetella pertussis toxin, islet-activating protein (IAP), was studied on adrenaline and PGE1-induced GTPase stimulation and on adrenaline-induced adenylate cyclase inhibition. Pretreatment of platelet membranes with IAP greatly reduced the adrenaline-induced inhibition, of the platelet adenylate cyclase. At similar concentrations of the toxin, stimulation of GTP hydrolysis caused by adrenaline was impaired. In contrast, pretreatment of platelet membranes with IAP had no effect on stimulation of GTP hydrolysis by the adenylate cyclase-stimulating agent, PGE1, both when studied alone or in combination with adrenaline. On the other hand, cholera toxin reduced the PGE1-induced GTPase stimulation but did not affect the adrenaline-stimulated GTP hydrolysis. The data indicate that there are two separate GTP-hydrolyzing systems in human platelet membranes and that cholera toxin and pertussis toxin selectively affect stimulation of GTP hydrolysis by hormones that stimulate and inhibit adenylate cyclase, respectively.

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Authors and Affiliations

  1. Pharmakologisches Institut der Universität Heidelberg, Im Neuenheimer Feld 366, D-6900, Heidelberg, Germany

    Klaus Aktories, Günter Schultz & Karl H. Jakobs

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  1. Klaus Aktories
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  2. Günter Schultz
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  3. Karl H. Jakobs
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Aktories, K., Schultz, G. & Jakobs, K.H. Islet-activating protein impairs α 2-adrenoceptor-mediated inhibitory regulation of human platelet adenylate cyclase. Naunyn-Schmiedeberg's Arch. Pharmacol. 324, 196–200 (1983). https://doi.org/10.1007/BF00503894

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  • DOI: https://doi.org/10.1007/BF00503894

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