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91.
We have studied problems associated with the application of the Cheng-Prusoff relationship to the estimation of atropine dissociation constants from isolated guinea-pig tracheal responses. The values obtained have been compared to dissociation constants derived using Schild analysis. It was observed that when either carbachol (an agonist of high efficacy) or pilocarpine (an agonist of low efficacy) was used the dissociation constants estimated for atropine using the Schild analysis were very similar to those estimated using the Cheng-Prusoff relationship. In these latter experiments the agonist concentration used was the EC80. When the agonist concentration used was increased to supramaximal concentrations (3-fold greater than the EC100) the dissociation constants derived were overestimations by approximately 10-fold. It is concluded that in certain circumstances the results obtained using both the Cheng-Prusoff relationship and Schild analysis are comparable. However, it is unlikely that the Cheng-Prusoff relationship is generally applicable and that Schild analysis is clearly preferable in determining antagonist dissociation constants. 相似文献
92.
Replacement of receptor cells in the hamster vomeronasal epithelium after nerve transection 总被引:1,自引:1,他引:0
Chemoreceptor cells in the vomeronasal and olfactory epithelium are
replaced following experimentally induced degeneration. This study analyzes
quantitatively the time course and degree of vomeronasal receptor cell
replacement. Unilateral transection of the vomeronasal nerves in adult
hamster was used to induce a retrograde degeneration of receptor cells in
the vomeronasal organ. Histological measurement of both number of receptor
cells and epithelial thickness were made for recovery times from 0 to 60
days. After nerve transection, there was a gradual degeneration of receptor
cells, the number decreasing to 50% of control by day 2 and 16% by day 6.
During days 7-15 maximum receptor cell replacement was observed. Cell
number increased rapidly and reached a peak on day 15. At recovery times of
40-60 days, cell number returned to the control level. Epithelial
thickness, however, decreased to 60-70% during the degeneration period
(days 4-6) and did not return to control levels. After 40-60 days
epithelial thickness remained at 70% of control. These results demonstrate
that vomeronasal receptor cells are replaced following degeneration, but
epithelial thickness does not return to control levels. These findings
suggest that the number of replacement cells is not limited by the reduced
thickness of the epithelium, and that recovery mechanisms may function to
restore an optimum number of receptor cells.
相似文献
93.
94.
Erik H. F. Wong Douglas W. Bonhaus Irene Wu Eric Stefanich Richard M. Eglen 《Journal of neurochemistry》1993,60(3):921-930
Abstract: RS-42358–197{(S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro-1H-benzo[de]isoquinolin-1-one hydrochloride} displaced the prototypic 5-hydroxytryptamine3 (5-HT3) receptor ligand [3H]quipazine in rat cerebral cortical membranes with an affinity (pKi) of 9.8 ± 0.1, while having weak affinity (pKi < 6.0) in 23 other receptor binding assays. [3H]RS-42358–197 was then utilized to label 5-HT3 receptors in a variety of tissues. [3H]RS-42358–197 labelled high-affinity and saturable binding sites in membranes from rat cortex, NG108–15 cells, and rabbit ileal myenteric plexus with affinities (KD) of 0.12 ± 0.01, 0.20 ± 0.01, and 0.10 ± 0.01 nM and densities (Bmax) of 16.0 ± 2.0, 660 ± 74, and 88 ± 12 fmol/mg of protein, respectively. The density of sites labelled in each of these tissues with [3H]RS-42358–197 was similar to that labelled with [3H]GR 65630, but was significantly less than that found with [3H]-quipazine. The binding of [3H]RS-42358–197 had a pharmacological profile similar to that of [3H]quipazine, as indicated by the rank order of displacement potencies: RS-42358–197 > (S)-zacopride > tropisetron > (R)-zacopride > ondansetron > MDL72222 > 5-HT. However, differences in 5-HT3 receptors of different tissues and species were detected on the basis of statistically significant differences in the affinities of phenylbiguanide, and 1-(m-chlorophenyl)biguanide when displacing [3H]RS-42358-197 binding. [3H]RS-42358–197 also labelled a population (Bmax= 91 ± 17 fmol/mg of protein) of binding sites in guinea pig myenteric plexus membranes, with lower affinity (KD= 1.6 ± 0.3 nM) than those in the other preparations. Moreover, the rank order of displacement potencies of 15 5-HT3 receptor ligands in guinea pig ileum was found not to be identical to that in other tissues. Binding studies carried out with [3H]RS-42358–197 have detected differences in 5-HT3 receptor binding sites in tissues of different species and further underscore the unique nature of the guinea pig 5-HT3 receptor. 相似文献
95.
96.
Muscarinic receptor ligands and their therapeutic potential. 总被引:4,自引:0,他引:4
Over the past year, the introduction of novel ligands has accelerated the classification of muscarinic receptor subtypes and has led to a better understanding of their physiological role. Important in this respect is the recent recognition of the exquisite selectivity of a series of snake toxins, enabling better definition of the muscarinic subtype 4 receptor. Moreover, several compounds, both agonists and antagonists, are progressing in advanced clinical trials for the treatment of several conditions, including Alzheimer's disease, pain, urinary incontinence and chronic obstructive pulmonary disease. 相似文献