Domoic Acid Attenuates the Adenosonine-5'- Triphosphate-Induced Increase in [Ca2+] i in Adult Cardiomyocytes
| Autor: | Satnam Nijjar, M. S. Nijjar, Grant N. Pierce, Naranjan S. Dhalla |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
0301 basic medicine
Pharmacology Kainic acid Nicardipine Glutamate receptor Biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Biochemistry chemistry Nifedipine medicine Biophysics Extracellular Neurotoxin Pharmacology (medical) Signal transduction Cardiology and Cardiovascular Medicine 030217 neurology & neurosurgery Intracellular medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology and Therapeutics. 4:159-165 |
| ISSN: | 1940-4034 1074-2484 |
| DOI: | 10.1177/107424849900400305 |
| Popis: | Background: Although domoic acid (DA), a shellfish neurotoxin, carries a negative surface charge at physiological pH like that of adenosine-5'-triphosphate (ATP), very little is known about its cellular effects. In view of the potentially significant role of extracellular ATP as a signaling molecule for increasing the intracellular concentration of Ca2+ ([Ca2+]i), we examined the possibility that DA may interfere with this signal transduction mechanism in the myocardium. Methods and Results: Cardiomyocytes were isolated from rat heart and loaded with Fura-2 to measure the [Ca2+]i. ATP produced a gradual rise in [Ca2+]i, reaching a peak level in 25- 30 seconds and declining thereafter. DA did not affect the [Ca2+]i in cardiomyocytes; however, it diminished the ATP-induced elevation in [Ca2+]i in a concentration-dependent manner. Kainic acid, an analogue of DA, had a similar effect but at a 25-fold higher concentration, whereas glutamate and aspartate did not modify the action of ATP. Well-known inhibitors of L-type voltage-sensitive Ca2+ channels, nifedipine and nicardipine, depressed the ATP- induced increase in [Ca2+ ]i, but DA did not produce additive effects with either of these agents. On the other hand, DA potentiated the KCl-induced increase in [Ca2+]i in quiescent cardiomyocytes and augmented the nicardipine-sensitive Ca2+ transients in electrically stimulated cardiomyocytes. Conclusions: These results suggest that DA may diminish the ATP-induced increase in [Ca 2+]i by inhibiting the ATP interaction with cardiomyocytes in a specific manner. |
| Databáze: | OpenAIRE |
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