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KMID : 0043319910140030271
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Archives of Pharmacal Research
1991 Volume.14 No. 3 p.271 ~ p.278
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Effect of Bay K 8644, a Calcium Channel Agonist, on Dog Cardiac Muscarinic Receptors
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Lee SW
Park YJ/Lee JS
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Abstract
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To investigate further whether the effects of the dihydropyridine (DHP) drugs on calcium channels are related to those of these drugs on muscarinic receptors, the binding characteristics of the DHP calcium channel agonist, Bay K 8644, on muscarinic receptors and calcium channels were compared to those of the DHP calcium channel antagonists, nicardipine and nimodipine in the dog cardiac sarcolemma. Bay K 8644, nicardipine and nimodipine inhibited the specific [3H]QNB binding with Ki values of 16.7mcM, 3.5mcM and 15.5mcM respectively. Saturation data of [3H]QNB binding in the presence of these DHP drugs showed this inhibition to be competitive. Bay K 8644, like nicardipine and nimodipine, blocked the binding of [3H]nitrendipine to the high affinity DHP binding sites, but atropine did not indicating that the muscarinic receptors and the DHP binding sites on calcium channels are distinct. The Ki value of Bay K 8644 for the DHP binding sites was 4nM. Nicardipine and nimodipine (Ki: 0.1-0.2nM) were at least 20 times more potent than Bay K 8644 in inhibiting [3H]nitrendipine binding. Thus, the muscarinic receptors were about 4000 times less sensitive than these high affinity DHP binding sites to Bay K 8644. These results suggest that the DHP calcium agonist Bay K 8644 binds directly to the muscarinic receptors but its interaction with the muscarinic receptors is not related to its binding to the DHP binding sites on calcium channels.
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KEYWORD
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