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PMID: 6140642 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Naunyn-Schmiedeberg's archives of pharmacology ·Vol. 324 ·No. 3 ·1983-11-00 ·Pages 196-200

Aktories K, Schultz G, Jakobs KH

Abstract

Human platelet adenylate cyclase is stimulated by prostaglandin E1 (PGE1) and inhibited by adrenaline acting via alpha 2-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.

MeSH Terms
Adenylate Cyclase Toxin Adenylyl Cyclase Inhibitors Alprostadil Bacterial Proteins/pharmacology Blood Platelets/enzymology Epinephrine/pharmacology GTP Phosphohydrolases/blood Guanosine Triphosphate/metabolism Humans In Vitro Techniques Pertussis Toxin Prostaglandins E/pharmacology Receptors, Adrenergic, alpha/drug effects,physiology Virulence Factors, Bordetella
Chemicals
Adenylate Cyclase Toxin Adenylyl Cyclase Inhibitors Bacterial Proteins Prostaglandins E Receptors, Adrenergic, alpha Virulence Factors, Bordetella Guanosine Triphosphate Pertussis Toxin GTP Phosphohydrolases Alprostadil Epinephrine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Aktories K
Schultz G
Jakobs K H
References (28)
28 references, click to expand
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Article Info
Journal
Naunyn-Schmiedeberg's archives of pharmacology
Abbr.
Naunyn Schmiedebergs Arch Pharmacol
ISSN
0028-1298
DOI
10.1007/BF00503894
Published
1983-11-00
Pages
196-200
Language
English
Region
Germany
NLM ID
0326264
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00503894 View journal details
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