Back to Search
Start Over
Defective signal transduction in platelets from cirrhotics is associated with increased cyclic nucleotides.
- Source :
-
Gastroenterology [Gastroenterology] 1993 Jul; Vol. 105 (1), pp. 148-56. - Publication Year :
- 1993
-
Abstract
- Background: Patients with advanced cirrhosis show defective platelet aggregation, which is dependent, at least in part, on intrinsic platelet abnormalities. The aim of this study was to evaluate the activating and inhibitory pathways of platelet signal transduction in cirrhotic patients.<br />Methods: Twelve cirrhotic patients and 12 control subjects participated in this study. Measurements were performed on washed platelets.<br />Results: Thrombin-stimulated inositol 1,4,5-trisphosphate production was reduced fivefold, and the increase in cytosolic calcium concentration was significantly lower in platelets from cirrhotic patients following stimulation with thrombin, platelet activating factor, or U-46619. In addition, the activity of the platelet Na+/H+ antiporter, evaluated after an acid load, was significantly lower in platelets from cirrhotic patients (0.90 +/- 0.19 vs. 1.37 +/- 0.16 delta pHi/min, P = 0.07). Cirrhotic patients also showed a significantly increased basal intraplatelet content of both 5'-cyclic adenosine monophosphate (cAMP) (2724 +/- 330 vs. 1561 +/- 258 fmol/10(8) platelets, P < 0.05) and 5'-cyclic guanosine monophosphate (cGMP) (217 +/- 18 vs. 159 +/- 29 fmol/10(8) platelets, P < 0.05).<br />Conclusions: Our results indicate that in platelets from cirrhotic patients, defective early signal transduction is associated with an increase in platelet cAMP and cGMP, thus revealing new mechanisms contributing to the defective platelet function in this disease.
- Subjects :
- Adult
Aged
Calcium metabolism
Carrier Proteins physiology
Epoprostenol biosynthesis
Female
Humans
Inositol Phosphates metabolism
Liver physiopathology
Liver Cirrhosis blood
Liver Cirrhosis physiopathology
Male
Middle Aged
Nitric Oxide metabolism
Sodium-Hydrogen Exchangers
Blood Platelets metabolism
Cyclic AMP blood
Cyclic GMP blood
Liver Cirrhosis metabolism
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 0016-5085
- Volume :
- 105
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 8390377
- Full Text :
- https://doi.org/10.1016/0016-5085(93)90020-d