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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 37 (1981), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Kinetic studies showed that under appropriate conditions, [3H]clonidine binds to two distinct receptor sites in calf cortex membranes. At 23°C, binding was obtained at a low-affinity site (dissociation constant, KD= 5.4 nm) and a high-affinity site (KD= 1.1 nm). In contrast, at 0°C, selective binding occurred to the low-affinity site only. Consequently, at 0°C, it was possible to evaluate the interaction of drugs with the low-affinity receptor directly. On the other hand, competition with the high-affinity receptor could be ascertained by generating displacement curves representing the differential between specific binding values obtained at 23 and 0°C. Guanine nucleotides selectively decreased binding to the high-affinity site without apparent influence on the low-affinity [3H]clonidine binding. The activities of various pharmacological agents at the low- and high-affinity clonidine receptors are discussed and compared with WB-4101 binding data.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: Pipecolic acid ; GABA ; Micro-iontophoresis ; GABA-B receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several previous studies have suggested a strong GABA-mimetic action of the endogenous brain imino acid, L-pipecolic acid (L-PA). In the present study, these observations were evaluated using electrophysiological and neurochemical methods. In contrast to published data our electrophysiological studies on rat cortical neuronesin situ showed only a weak, but bicuculline-sensitive depressant action of L-PA on cortical neurones. Furthermore, L-PA proved to have no affinity for any of the three components of the GABA-benzodiazepine-chloride channel receptor complex. However, using a modification of published methods a weak affinity for the GABA-B receptor site was demonstrated (IC50=1.8×10−3 M). L-PA showed no anticonvulsive activity in several tests; in particular, it did not protect mice from seizures induced by inhibition of L-glutamate-1-decarboxylase (EC 4.1.1.15: GAD). L-PA had a very weak action on brain GABA levels of mice, and did not modify the rate of GABA synthesis. In conclusion, these results are not compatible with a strongin vivo interaction between L-PA and GABA-mediated inhibitory transmission.
    Type of Medium: Electronic Resource
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