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Two distinct receptors for ATP can be distinguished in Swiss 3T6 mouse fibroblasts by their desensitization

F A Gonzalez1, E Bonapace, I Belzer

  • 1Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853.

Insights

Extracellular adenosine triphosphate (ATP) triggers calcium efflux in mouse fibroblasts, suggesting a receptor-mediated process. Researchers selectively desensitized this calcium pathway, indicating multiple ATP receptors on cells.

Area of Science:

  • Cell biology
  • Biochemistry
  • Molecular pharmacology

Background:

  • Extracellular adenosine triphosphate (ATP) is known to regulate cellular processes in various cell types.
  • ATP-induced responses in Swiss 3T6 mouse fibroblasts, such as calcium efflux and plasma membrane permeabilization, are mediated by purinergic receptors.
  • These ATP-mediated processes are known to be subject to desensitization upon prolonged exposure to ATP.

Purpose of the Study:

  • To investigate the desensitization characteristics of ATP-stimulated calcium efflux in Swiss 3T6 fibroblasts.
  • To determine if the calcium mobilization pathway can be selectively desensitized independently of ATP-induced plasma membrane permeabilization.
  • To provide evidence for the existence of multiple ATP receptors (purinoceptors) in Swiss 3T6 cells.

Main Methods:

  • Utilized Swiss 3T6 mouse fibroblasts for experimental studies.
  • Applied extracellular adenosine triphosphate (ATP) to stimulate cellular responses.
  • Monitored calcium efflux and plasma membrane permeabilization.
  • Investigated desensitization by pre-exposing cells to ATP.

Main Results:

  • Extracellular ATP stimulates calcium efflux from Swiss 3T6 fibroblasts.
  • Cells exhibited desensitization to ATP-induced calcium efflux after prior exposure to the nucleotide.
  • Selective desensitization of the calcium mobilization pathway was achieved without impacting ATP-induced plasma membrane permeabilization.
  • Data support the presence of multiple distinct ATP receptors on Swiss 3T6 cells.

Conclusions:

  • The desensitization of ATP-induced calcium efflux supports a receptor-mediated mechanism.
  • Swiss 3T6 cells possess at least two distinct purinoceptors mediating different cellular responses.
  • These findings highlight the complexity of purinergic signaling and receptor heterogeneity in fibroblasts.

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