| Autor: |
Kumari, Rajendra, Goh, Gareth, Ng, Leong L., Boarder, Michael R. |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology; Dec2003, Vol. 140 Issue 7, p1169-1176, 8p, 7 Graphs |
| Abstrakt: |
1 It has previously been shown that ATP and UTP stimulate P2Y receptors in vascular smooth muscle cells (VSMCs), but the nature of these receptors, in particular the contribution of P2Y[sub2] and P2Y[sub4] subtypes, has not been firmly established, Here we undertake a further pharmacological analysis of ³ H] inositol polyphosphate responses to nucleotides in cultured rat VSMCs. 2 ATP generated a response that was partial compared to UTP, as reported earlier. 3 In the presence of a creatine phosphokinase (CPK) system for regenerating nucleoside triphosphates. the response to ATP was increased, the response to UTP was unchanged, and the difference between UTP and ATP concentration response curves disappeared. Chromatographic analysis showed that ATP was degraded slightly faster than UTP. 4 The response to UDP was always smaller than that to UTP. but with a shallow slope and a high potency component. In the presence of hexokinase (which prevents the accumulation of ATP/UTP from ADP/UDP) the maximum response to UDP was reduced and the high-potency component of the curve was retained. By contrast, the response to ADP was weaker throughout in the presence of hexokinase. 5 ATPγS was an effective agonist with a simitar EC[sub50] to UTP. but with a lower maximum. 1TP was a weak agonist compared with UTP. 6 Suramin was an effective antagonist of the response to UTP (pA[sub2] = 4.48), but not when ATP was the agonist. However, suramin was an effective antagonist (pA[sub2] = 4.45) when stimulation with ATP was in the presence of the CPK regenerating system. 7 Taken together with the results of others, these findings indicate that the response of cultured rat VSMCs to UTP and to ATP is predominantly at the P2Y[sub2] receptor, and that there is also a response to UDP at the P2Y[sub6] receptor. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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