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Mechanisms of the Potentiation by Adenosine of Adenosine Triphosphate–Induced Calcium Release in Tracheal Smooth-Muscle Cells
- Source :
- American Journal of Respiratory Cell and Molecular Biology. 21:30-36
- Publication Year :
- 1999
- Publisher :
- American Thoracic Society, 1999.
-
Abstract
- The effects of concomitant P1-receptor stimulation on peak intracellular Ca2+ release by extracellular adenosine 5'-triphosphate (ATP) and 5-hydroxytryptamine (5-HT) were investigated in cultured airway smooth-muscle (ASM) cells. The results show that peak Ca2+ release to ATP is enhanced by preincubation with adenosine (ADO) and with the specific A3 receptor agonist 1-Deoxy-1-(6-([(3-iodophenyl)methyl] amino)-9H-purin-9-yl)-N-methyl-beta-D-ribofuranuronamide (1B-MECA). The response to 5-HT, a smooth-muscle contractile agonist, was also enhanced after preincubation with ADO. Further measurements showed that this enhancement of the response to ATP was dependent on extracellular calcium because it was abolished by the removal of Ca2+ from the extracellular fluid and by incubation with the calcium channel blocker nifedipine. In addition, there was no difference between the levels of total inositol phosphates measured in the presence of ATP alone or of ADO + ATP. AACOCF3, a specific blocker of phospholipase A2, decreased the peak Ca2+ response to ATP and abolished the enhanced response to ATP and 5-HT produced by ADO. We conclude that stimulation of P1 and P2 receptors in ASM cells activates not only phospholipase C but also phospholipase A2. The enhancement of ATP-induced and 5-HT-induced Ca2+ release is due to Ca2+ influx from the extracellular fluid through a Ca2+ channel presumably modulated by arachidonic acid. These data show that endogenous ADO may modulate airway hyperresponsiveness by enhancing the ASM response to contractile agonists.
- Subjects :
- Pulmonary and Respiratory Medicine
Agonist
Serotonin
medicine.medical_specialty
Adenosine
Nifedipine
medicine.drug_class
Clinical Biochemistry
chemistry.chemical_element
Arachidonic Acids
Calcium
Adenosine A1 receptor
chemistry.chemical_compound
Adenosine Triphosphate
Internal medicine
Extracellular fluid
medicine
Extracellular
Animals
Enzyme Inhibitors
Molecular Biology
Cells, Cultured
Dose-Response Relationship, Drug
Drug Synergism
Muscle, Smooth
Cell Biology
Purinergic signalling
Rats, Inbred F344
Rats
Trachea
Endocrinology
chemistry
Biophysics
Adenosine triphosphate
medicine.drug
Subjects
Details
- ISSN :
- 15354989 and 10441549
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory Cell and Molecular Biology
- Accession number :
- edsair.doi.dedup.....9c7554d98b0862a8611db544c9f4f65d