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  • 1
    Electronic Resource
    Electronic Resource
    Phentolamine blocks presynaptic serotonin autoreceptors in rabbit and rat brain cortex (1989)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 52-61 
    Details
    ISSN: 1432-1912
    Keywords: Rabbit brain cortex ; Rat brain cortex ; Serotonin release ; Presynaptic serotonin autoreceptors ; Presynaptic α2-adrenoceptors ; Phentolamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Possible antagonist effects of phentolamine at presynaptic serotonin autoreceptors were studied in slices of the occipito-parietal cortices of the rabbit and the rat. The slices were preincubated with 3H-serotonin and then superfused and stimulated electrically with single pulses or pulse trains. Nitroquipazine 1 μmol/l, a compound that inhibits the high affinity neuronal uptake of serotonin, was present in the superfusion medium in all one pulse-experiments as well as in experiments in which the effect of unlabelled serotonin was examined. In rabbit cortical slices, unlabelled serotonin reduced the single pulse-evoked overflow of tritium. Its concentrationresponse curve was not changed by the selective α2-adrenoceptor antagonist idazoxan 1 μmol/l but was shifted to the right by phentolamine 1 and 10 μmol/l. Phentolamine 10 μmol/l also shifted to the right the concentration-inhibition curve of the selective 5-HT1-receptor agonist 5-carboxamidotryptamine. When the slices were stimulated by trains of 30 pulses at 3 Hz, phentolamine 1 and 10 μmol/l but not 0.1 μmol/l increased the evoked overflow of tritium, the maximal increase amounting to 178%; its effect was enhanced in the presence of nitroquipazine 1 μmol/l plus idazoxan 10 μmol/l (a drug combination that, when given alone, slightly increased the evoked overflow of tritium). The serotonin receptor antagonist metitepin at concentrations of 0.01–1 μmol/l also increased the overflow of tritium elicited by 30 pulses/3 Hz, the maximal increase amounting to 280%; its effect was potentiated in the presence of nitroquipazine 1 μmol/l plus idazoxan 10 μmol/l but was abolished or almost abolished in the presence of nitroquipazine 1 μmol/l plus phentolamine 10 μmol/l (a drug combination that, given alone, greatly increased the evoked overflow of tritium). When slices were stimulated by trains of 360 pulses at 3 Hz, there was no apparent antagonism of phentolamine 10 μmol/l against the inhibitory effect of unlabelled serotonin. In rat brain cortex slices, unlabelled serotonin reduced the overflow of tritium elicited by 4 pulses delivered at 100 Hz. Again, phentolamine 10 μmol/l shifted the concentration-response curve to the right. It is concluded that phentolamine blocks presynaptic serotonin autoreceptors in rabbit and rat brain cortex with pA2 values of 6.44 and 5.95, respectively. Previous failures to detect the antagonistic effect against exogenous agonists were probably due to stimulation conditions that led to marked endogenous autoinhibition of serotonin release. At least the major part of the increase by phentolamine of the release of serotonin is due to autoreceptor blockade rather than blockade of the presynaptic a2-adrenoceptors at the cortical serotoninergic axons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169207
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Serotonin uptake blockers influence serotonin autoreceptors by increasing the biophase concentration of serotonin and not through a “molecular link” (1990)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 342 (1990), S. 363-370 
    Details
    ISSN: 1432-1912
    Keywords: Rabbit brain cortex ; Rat hypothalamus ; Serotonin release ; Presynaptic serotonin autoreceptors ; Serotonin uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The mechanism of the attenuation, by serotonin uptake blockers, of the release-inhibiting effect of exogenous serotonin autoreceptor agonists was studied in rabbit brain cortex and rat hypothalamus slices. The slices were preincubated with 3H-serotonin and then superfused and stimulated electrically. In rabbit brain slices stimulated by trains of 4 pulses at 100 Hz, 5-carboxamidotryptamine and 5-methoxytryptamine reduced the evoked overflow of tritium, and their concentration-response curves were not changed by any of three serotonin uptake inhibitors, namely citalopram, fluvoxamine and 6-nitroquipazine. In contrast, when the slices were stimulated by trains of 10 pulses at 0.033 Hz, fluvoxamine shifted the concentration-response curve of 5-methoxytryptamine to the right. Experiments with the autoreceptor antagonist metitepine indicated that little, if any, endogenous autoinhibitory tone developed in the course of trains of 4 pulses/100 Hz, irrespective of the absence or presence of uptake inhibitors, as well as during trains of 10 pulses/0.033 Hz in the absence of uptake inhibitors, whereas marked autoinhibition developed when 10 pulses/0.033 Hz were applied in the presence of fluvoxamine. In rat hypothalamic slices stimulated by trains of 4 pulses at 100 Hz, citalopram also failed to change the concentration-response curve of 5-methoxytryptamine. These results indicate that serotonin uptake blockers attenuate the effect of exogenous autoreceptor agonists by an increase in the biophase concentration of released serotonin and, hence, in endogenous autoinhibitory tone, and not by some direct “molecular link” unrelated to the biophase concentration of released serotonin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169450
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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