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KMID : 0043319870100040212
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Archives of Pharmacal Research
1987 Volume.10 No. 4 p.212 ~ p.218
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Agonist-induced Desensitization of Muscarinic Acetylcholine Receptor in Rat Brain
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Lee JH
El Fakahany EE
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Abstract
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Intact brain cell aggregates were dissociated from adult rat brains without cerebellum using a sieving technique. This preparation was used to elucidate the binding characteristics of agonist to muscarinic acetylcholine receptors (mAchR) in brain. Incubation of cells with carbamylcholine (carbachol) was shown agonist-induced receptor down-regulation depending on the concentration of agonist, not depending on the incubation time. This effect of carbachol was due to a reduction in the maximal binding capacity (Bmax) to the mAchR without decreasing the affinity of the remaining receptors in incubation at 37oC but was not apparent in incubation at 15oC. In addition, it was abolished when the receptors were blocked by atropine. The decline in (3H)N-methylscopolamine((3H)NMS) binding induced by agonist was reflected as a significant reduction in the receptor density with no change in receptor affinity, suggesting that ’’true’’ receptor down-regulation takes place. Moreover, when the receptors were labeled with the lipophilic antagonist (3H)quinuclidinyl benzilate ((3H)QNB) insted of the hydrophilic ligand (3H)NMS, the magnitude of the observed receptor down-regulation was significantly lower in case of the former than the latter. This suggests that exposure of intact brain cells to muscarinic agonists might induce a slight degree of accumulation of receptors in intracellular sites before the receptors are actually degraded.
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