Does thrombin stimulation of human platelets proceed via a simultaneous Na/sup +/-H/sup +/ exchange
Thrombin stimulation of human platelets initiates a membrane depolarization attributable to a Na/sup +/ influx into, and an alkalinization of, the cytoplasm, both of which follow a similar rapid time scale and thrombin dose dependence. These responses precede secretion of the contents of dense granules (serotonin) and, after 1 min, of lysosomes (..beta..-glucuronidase). These markers have been used to determine whether the Na/sup +/ influx and H/sup +/ efflux are sequential or simultaneous. They have examined these parameters in D/sub 2/O-Hepes buffers. NMR evidence indicates that equilibration is rapid, and virtually complete within the 3 minute pre-stimulation platelets equilibration period. The rate of depolarization is 70-80% slower in D/sub 2/O than in H/sub 2/O. The time to reach maximal depolarization is 5-10 sec longer, the extent of depolarization 60% inhibited, and the (H/sup +/) change 85-100% inhibited. The serotonin secretion is unaltered, and the ..beta..-glucuronidase secretion is 130-180% enhanced. 10/sup -4/ M amiloride inhibits Na/sup +/ influx, i.e. depolarization, and the pH change completely. Adjustment to pH/sub i/ 7.3 with NH/sub 4/Cl led to a 30-80% enhanced ..beta..-glucuronidase release upon thrombin exposure. These results suggest that the Na/sup +/ and H/sup +/ fluxes across the platelet membrane occur sequentially, the Na/sup +/ occurring first. Furthermore, granule secretion, previously shown by us to be independent of the existent Na/sup +/ gradient, depends on the cytoplasmic K/sup +/ and H/sup +/ concentrations.
- Research Organization:
- Boston Univ. School of Medicine, MA
- OSTI ID:
- 6851430
- Report Number(s):
- CONF-8604222-; TRN: 87-005722
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
BLOOD PLATELETS
BLOOD COAGULATION
CELL MEMBRANES
DEPOLARIZATION
SEROTONIN
SECRETION
THROMBIN
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
CATIONS
DEUTERIUM
DOSE-RESPONSE RELATIONSHIPS
HYDROGEN COMPOUNDS
ION EXCHANGE
MAN
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
SODIUM COMPOUNDS
TRACER TECHNIQUES
ALKALI METAL COMPOUNDS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CONSTITUENTS
CHARGED PARTICLES
COAGULANTS
DRUGS
ENZYMES
HEMATOLOGIC AGENTS
HEMOSTATICS
HETEROCYCLIC COMPOUNDS
HYDROGEN ISOTOPES
HYDROLASES
HYDROXY COMPOUNDS
INDOLES
IONS
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAGNETIC RESONANCE
MAMMALS
MATERIALS
MEMBRANES
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HYDROLASES
PRIMATES
PYRROLES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RESONANCE
SERINE PROTEINASES
SPECTRA
STABLE ISOTOPES
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
550600 - Medicine