Inhibition by islet-activating protein, pertussis toxin, of P2-purinergic receptor-mediated iodide efflux and phosphoinositide turnover in FRTL-5 cells
Exposure of FRTL-5 thyroid cells to ATP (1 microM to 1 mM) resulted in the stimulation of I- efflux in association with the induction of inositol trisphosphate production and intracellular Ca2+ mobilization. Nonhydrolyzable ATP derivatives, ADP and GTP, were also as effective in magnitude as ATP, whereas neither AMP nor adenosine exerted significant effect on I- efflux, suggesting a P2-purinergic receptor-mediated activation of I- efflux. Treatment of the cells with the islet-activating protein (IAP) pertussis toxin, which ADP-ribosylated a 41,000 mol wt membrane protein, effectively suppressed the phosphoinositide response to ATP in addition to ATP-dependent I- efflux at agonist concentrations below 10 microM. In contrast, the I- efflux stimulated by TSH, A23187, or phorbol myristate acetate was insusceptible to IAP. The IAP substrate, probably GTP-binding protein, is hence proposed to mediate the activation of P2-purinergic receptor-linked phospholipase-C in FRTL-5 cells. However, the responses to ATP, its nonhydrolyzable derivatives, or ADP at the higher agonist concentrations, especially above 100 microM, were only partially inhibited by IAP, even though the IAP substrate was totally ADP ribosylated by the toxin. The responses to GTP in the whole concentration range tested were not influenced by IAP treatment. Thus, signals arising from the P2-receptor might be transduced to phospholipase-C by two different pathways, i.e. IAP-sensitive and insensitive ones, and result in the stimulation of I- efflux.
- Research Organization:
- Gunma Univ., Maebashi (Japan)
- OSTI ID:
- 6834863
- Journal Information:
- Endocrinology; (United States), Vol. 123:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
IODIDES
BIOSYNTHESIS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PHOSPHOLIPIDS
ADP
ATP
CALCIUM
INHIBITION
MOLECULAR WEIGHT
RATS
THYROID CELLS
TOXINS
ALKALINE EARTH METALS
ANIMAL CELLS
ANIMALS
ANTIGENS
CARCINOGENS
ELEMENTS
ESTERS
HALIDES
HALOGEN COMPOUNDS
IODINE COMPOUNDS
LIPIDS
MAMMALS
MATERIALS
METALS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
RODENTS
SYNTHESIS
TOXIC MATERIALS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology