Rat brain and heart muscarinic receptors: modification with tetranitromethane |
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| Authors: | D Gurwitz M Sokolovsky |
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| Institution: | 1. Department of Anesthesiology, Pharmacology and Therapeutics, and Djavad Mowafaghian Centre for Brain Health, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada;2. Department of Medical Sciences, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi 127788, United Arab Emirates;3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt;4. University of Ottawa Brain and Mind Research Institute, Ottawa, Ontario K1H 8M5, Canada;5. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada;6. Department of Neuroscience, Faculty of Health Sciences, Carleton University, Ottawa, Ontario K1S 5B6, Canada;1. Department of Physiology, College of Medicine and Neuroscience Research Institute, Korea University, Seoul, Republic of Korea;2. Department of Physical Therapy, Baekseok University, Cheonan, Republic of Korea;1. College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 610032, China;2. Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Science, Chengdu, 610000, China;3. Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610000, China |
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| Abstract: | Tetranitromethane at a concentration of 50 microM modifies the muscarinic receptors in membrane preparations from rat striatum, hippocampus and heart atrium, but not from the rat brain stem. While the binding of antagonists is only slightly altered, the modified receptor possesses an increased affinity of up to 8-fold for 3H]-acetylcholine binding to the high affinity state. This effect is absent if the nitration is carried out in the presence of an antagonist, but not in the presence of an agonist. The affinity for carbamylcholine is increased for both the high and the low affinity state of the receptor, as is evident from its ability to compete with a labeled antagonist. In addition, the proportion of binding sites (alpha) exhibiting the high affinity state for 3H]-acetylcholine or for carbamylcholine is increased upon nitration. This increase cannot be protected against by an antagonist, and is enhanced when nitration takes place in the presence of an agonist. With the agonists oxotremorine and 3H]-oxotremorine-M only the latter effect (i.e., increase in alpha) is observed following nitration, while their dissociation constants for the receptor are unchanged. Data are discussed with respect to the proposed existence of subtypes of muscarinic receptors, as well as the importance of the agonist chosen for studies of ligand-receptor interactions. |
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