Incubation of 1321N1 human astrocytoma cells with carbachol resulted in a rapid loss of binding of [3H]N-methylscopolamine ([3H]NMS) to muscarinic cholinergic receptors measured at 4 degrees C on intact cells; loss of muscarinic receptors in lysates from the same cells measured with [3H]quinuclidinyl benzilate [( 3H]QNB) at 37 degrees C occurred at a slower rate. Upon removal of agonist from the medium, the lost [3H]NMS binding sites measured on intact cells recovered with a t1/2 of approximately 20 min, but only to the level to which [3H]QNB binding sites had been lost; no recovery of "lost" [3H]QNB binding sites occurred over the same period. Based on these data and the arguments of Galper et al. (Galper, J. B., Dziekan, L. C., O'Hara, D. S., and Smith, T. W. (1982) J. Biol. Chem. 257, 10344-10356) regarding the relative hydrophilicity of [3H]NMS versus [3H]QNB, it is proposed that carbachol induces a rapid sequestration of muscarinic receptors that is followed by a loss of these receptors from the cell. These carbachol-induced changes are accompanied by a change in the membrane form of the muscarinic receptor. Although essentially all of the muscarinic receptors from control cells co-purified with the plasma membrane fraction on sucrose density gradients, 20-35% of the muscarinic receptors from cells treated for 30 min with 100 microM carbachol migrated to a much lower sucrose density. This conversion of muscarinic receptors to a "light vesicle" form occurred with a t1/2 approximately 10 min, and reversed with a t1/2 approximately 20 min. In contrast to previous results in this cell line regarding beta-adrenergic receptors (Harden, T. K., Cotton, C. U., Waldo, G. L., Lutton, J. K., and Perkins, J. P. (1980) Science 210, 441-443), agonist binding to muscarinic receptors in the light vesicle fraction obtained from carbachol-treated cells was still regulated by GTP. One interpretation of these data is that agonists induce an internalization of muscarinic receptors with the retention of their functional interaction with a guanine nucleotide regulatory protein.
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Sci Rep
January 2025
Department of Pharmacology and Experimental Therapeutics; MS 1015, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Education Building; Room 282E, 3000 Arlington Ave, Toledo, OH, 43614, USA.
We previously demonstrated that the inability of primary endothelial cilia to sense fluid shear stress can lead to nitric oxide (NO) deficiency and cause hypertension (HTN). Decreased biosynthesis of NO contributes to cerebral amyloid angiopathy in Alzheimer's disease (AD) patients through increased deposition of amyloid beta (Aβ). However, the molecular mechanisms underlying the pathogenesis of HTN and AD are incompletely understood.
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Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Fujian, 361000, China.
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Acta Naturae
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Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997 Russian Federation.
The secreted human protein SLURP-2 is a regulator of epithelial homeostasis, which enhances the viability and migration of keratinocytes. The targets of SLURP-2 in keratinocytes are nicotinic and muscarinic acetylcholine receptors. This work is devoted to the search for the SLURP-2 functional regions responsible for enhancing keratinocyte viability and migration.
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Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy.
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Lab. Neurobiology of Sleep-Wakefulness Cycle, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia.
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