| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Physiology, University of Massachusetts Medical School, Worcester 01605.
1. The desensitization of nicotinic acetylcholine receptors on the PC12 sympathetic cell line was investigated by using a 22Na+ influx assay to measure receptor activation. 2. The rate of desensitization was dependent on temperature and at 4 degrees C two distinct kinetic phases were readily discernible: a rapid phase that was characterized by rate constants that were dependent on the chemical nature and concentration of the agonist, and a slower phase that was characterized by rate constants that were less dependent on these. 3. For acetylcholine, carbamylcholine and l-nicotine, the equilibrium desensitization parameter, Kdes, the concentration that produces half-maximal desensitization, was determined and compared with the corresponding value for Kact, the concentration that results in a half-maximal increase in the permeability response. For each agonist, the value of Kdes was found to be lower than Kact, a result to be expected if desensitization is associated with a higher-affinity state of the receptor than that associated with ion channel activation. Thus, extensive receptor desensitization can occur even at agonist concentrations that do not produce appreciable channel activation. Both activation and desensitization functions exhibited positive cooperativity so that each function occurs over a narrow range of agonist concentrations. 4. Following removal of the agonist, recovery from desensitization was reversible and occurred by two distinct kinetic phases characterized by rate constants that were independent of the chemical nature and concentration of the agonist that produced the desensitization. The relative contribution of each kinetic phase of recovery was, however, dependent on the duration of prior exposure to agonist. Following short incubation periods with agonist, most of the receptors were in a rapidly recovering state. With increasing duration of exposure, progressively more of the receptors were converted to a desensitized state that recovered more slowly. 5. The rate constants associated with the two kinetic phases of recovery were dependent on the recovery temperature. Following the initial rapid phase of desensitization, recovery at 4 degrees C was characterized by a time constant, t1/2, of 1.9 min, a value that was about 3-fold greater than that observed at 22 degrees C. The rate of recovery of the desensitized state achieved following equilibrium exposures to agonists was considerably more temperature dependent: recovery of this desensitized state was characterized at 4 degrees C by a t1/2 of 62 min that was about 37-fold greater than that at 22 degrees C.(ABSTRACT TRUNCATED AT 400 WORDS)
This article has been cited by other articles:
|
|
 |
|
  X. Guo and R. A. J. Lester Regulation of Nicotinic Acetylcholine Receptor Desensitization by Ca2+ J Neurophysiol, January 1, 2007; 97(1): 93 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Gentry, L. H. Wilkins Jr., and R. J. Lukas Effects of Prolonged Nicotinic Ligand Exposure on Function of Heterologously Expressed, Human alpha 4beta 2- and alpha 4beta 4-Nicotinic Acetylcholine Receptors J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 206 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Katsura, Y. Mohri, K. Shuto, Y. Hai-Du, T. Amano, A. Tsujimura, M. Sasa, and S. Ohkuma Up-regulation of L-type Voltage-dependent Calcium Channels after Long Term Exposure to Nicotine in Cerebral Cortical Neurons J. Biol. Chem., March 1, 2002; 277(10): 7979 - 7988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Meyer, Y. Xiao, and K. J. Kellar Agonist Regulation of Rat alpha 3beta 4 Nicotinic Acetylcholine Receptors Stably Expressed in Human Embryonic Kidney 293 Cells Mol. Pharmacol., September 1, 2001; 60(3): 568 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Narahashi, C. P. Fenster, M. W. Quick, R. A. J. Lester, W. Marszalec, G. L. Aistrup, D. B. Sattelle, B. R. Martin, and E. D. Levin Symposium Overview: Mechanism of Action of Nicotine on Neuronal Acetylcholine Receptors, from Molecule to Behavior Toxicol. Sci., October 1, 2000; 57(2): 193 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Lu, M. J. Marks, and A. C. Collins Desensitization of Nicotinic Agonist-Induced [3H]gamma -Aminobutyric Acid Release from Mouse Brain Synaptosomes Is Produced by Subactivating Concentrations of Agonists J. Pharmacol. Exp. Ther., December 1, 1999; 291(3): 1127 - 1134. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. P. Fenster, T. L. Whitworth, E. B. Sheffield, M. W. Quick, and R. A. J. Lester Upregulation of Surface alpha 4beta 2 Nicotinic Receptors Is Initiated by Receptor Desensitization after Chronic Exposure to Nicotine J. Neurosci., June 15, 1999; 19(12): 4804 - 4814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Reitstetter, R. J. Lukas, and R. Gruener Dependence of Nicotinic Acetylcholine Receptor Recovery from Desensitization on the Duration of Agonist Exposure J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 656 - 660. [Abstract] [Full Text]
|
|
|
|
|
|
C. P. Fenster, M. L. Beckman, J. C. Parker, E. B. Sheffield, T. L. Whitworth, M. W. Quick, and R. A. J. Lester Regulation of alpha 4beta 2 Nicotinic Receptor Desensitization by Calcium and Protein Kinase C Mol. Pharmacol., March 1, 1999; 55(3): 432 - 443. [Abstract] [Full Text]
|
|
|
|
|
|
S. K. Mahata, M. Mahata, R. J. Parmer, and D. T. O'Connor Desensitization of Catecholamine Release. THE NOVEL CATECHOLAMINE RELEASE-INHIBITORY PEPTIDE CATESTATIN (CHROMOGRANIN A344-364) ACTS AT THE RECEPTOR TO PREVENT NICOTINIC CHOLINERGIC TOLERANCE J. Biol. Chem., January 29, 1999; 274(5): 2920 - 2928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Paradiso and P. Brehm Long-Term Desensitization of Nicotinic Acetylcholine Receptors Is Regulated via Protein Kinase A-Mediated Phosphorylation J. Neurosci., November 15, 1998; 18(22): 9227 - 9237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Khiroug, E. Sokolova, R. Giniatullin, R. Afzalov, and A. Nistri Recovery from Desensitization of Neuronal Nicotinic Acetylcholine Receptors of Rat Chromaffin Cells Is Modulated by Intracellular Calcium through Distinct Second Messengers J. Neurosci., April 1, 1998; 18(7): 2458 - 2466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Fenster, M. F. Rains, B. Noerager, M. W. Quick, and R. A. J. Lester Influence of Subunit Composition on Desensitization of Neuronal Acetylcholine Receptors at Low Concentrations of Nicotine J. Neurosci., August 1, 1997; 17(15): 5747 - 5759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Han, J. Zhang, and M. M. Slaughter Partition of Transient and Sustained Inhibitory Glycinergic Input to Retinal Ganglion Cells J. Neurosci., May 15, 1997; 17(10): 3392 - 3400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Genazzani, R. M. Empson, and A. Galione Unique Inactivation Properties of NAADP-sensitive Ca[IMAGE] Release J. Biol. Chem., May 17, 1996; 271(20): 11599 - 11602. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
