Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats
Thrombin-induced aggregation and serotonin release were markedly enhanced in platelets from spontaneously hypertensive rats (SHR) when compared with those from normotensive Wistar-Kyoto rats (WKY). Since phosphoinositides are involved in calcium-mediated platelet responses, the metabolism of these lipids was investigated in SHR and WKY by using /sup 32/P-labeled quiescent platelets. In unstimulated cells, both the rate and extent of /sup 32/P incorporation into individual inositol-containing phospholipids and phosphatidic acid were identical in SHR and WKY. This finding suggests that the pool size and basal turnover of phosphoinositides did not differ between the two strains. In contrast, early thrombin-induced phosphoinositide metabolism, when monitored as changes in (/sup 32/P)phosphatidic acid, was significantly higher in SHR than in WKY. For example, a 20-second exposure to thrombin, 0.3 U/ml, induced the formation of 1.6 times more (/sup 32/P)phosphatidic acid in SHR than in WKY. These results provide evidence for a leftward shift of the dose-response and time-course curves of thrombin-induced (/sup 32/P)phosphatidic acid formation in SHR. Moreover, the extent of the difference between SHR and WKY was independent of the extracellular calcium concentration. Following thrombin stimulation, (/sup 32/P)phosphatidic acid formation likely reflects the initial agonist-receptor interaction; therefore, these results suggest that phospholipase C activity is enhanced in platelets of SHR and that the hypersensitivity of phospholipase C in SHR may play a role in the overall alteration of cell calcium handling and, hence, in the platelet responses of SHR.
- Research Organization:
- Institut National de la Sante et de la Recherche Medicale (INSERM U7), Paris, France
- OSTI ID:
- 5666514
- Journal Information:
- Hypertension (Dallas); (United States), Journal Name: Hypertension (Dallas); (United States) Vol. 10:5; ISSN HPRTD
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METALS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGICAL VARIABILITY
BLOOD
BLOOD CELLS
BLOOD COAGULATION
BLOOD PLATELETS
BODY FLUIDS
CALCIUM
CARBOXYLESTERASES
CARDIOVASCULAR DISEASES
COAGULANTS
DAYS LIVING RADIOISOTOPES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELEMENTS
ENZYME ACTIVITY
ENZYMES
ESTERASES
ESTERS
GENETIC VARIABILITY
HEMATOLOGIC AGENTS
HEMOSTATICS
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
HYPERTENSION
INDOLES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPASE
LIPIDS
MAMMALS
MATERIALS
METABOLISM
METALS
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PATHOGENESIS
PEPTIDE HYDROLASES
PHOSPHOLIPIDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PYRROLES
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SECRETION
SERINE PROTEINASES
SEROTONIN
SYMPATHOMIMETICS
SYMPTOMS
THROMBIN
TRACER TECHNIQUES
TRYPTAMINES
VASCULAR DISEASES
VERTEBRATES