Erowid References Database
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Macdermot J, Higashida H.
“Independent Regulation of Receptor-Mediated Cell Depolarization and Adenylate Cyclase by 5-Hydroxytryptamine (Serotonin) in Neuroblastoma Hybrid Cells”.
Biochem. Soc. Trans.. 1979;7(4):690-671.
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Abstract
5-Hydroxytryptamine (serotonin) accelerates or inhibits spontaneous neuronal firing in many areas of the brain (Bloom et al., 1972. Responses are predominantly inhibitory and are mediated through both pre- and post-synaptic receptors, which have different regional distributions in brain and differ in their pharmacological properties (Haigler & Aghajanian, 1974; Aghaianian & Haigler, 1975). Stimulation of adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.—. 1; 1 ] by 5-hydroxytryptarnine has been demonstrated in mammalian brain (Enjalbert et Al., 1978a,b) and is mediated by post-synaptic 5-hydroxyryptamine receptors (Enjalbert et al., 1978a). The possibility of multiple 5-hydroxytryptamine-receptor functions being expressed in cultured neuro blastoma hybrid cells was investigated. Cholinergic hybrid cell lines were screened for 5-hydroxytryptamine-dependent regulation of adenylate cyclase and acetylcholine release. Results are presented for the NG108-15 neuroblastoma x glioma hybrid (Klee Nirenberg, 1974) and the NCB-20 neuroblastoma x brain of foetal Chinese hamster hybrid (Minna et al., 1975). Electrophysio]ogical data were obtained by using methods described previously (Christian et al., 1978). Iontophoretic application of 5-hydroxytryptamine produced depolarizing responses inNG108-15 and TCB-20 hybrid cells -pith the generation of action potentials, which were neitherinhibited nor mimicked bv LSD. Results in NG108-15 cells confirmed the findings of Christian et aL (1978). Repeated application of 5-hydroxytryptamine at a frequency of 0.51Hz desensitized the receptors with a decrease in the depolarizing response and eventual loss of action potentials. Both hybrid cell lines are synaptically competent-and formed stable synapses with myotubes in primary cultures from Fisher rat hind limb. Application of 5-hydroxytryptamine to the hybrid cells in co-culture produced an increase in acetvlcholine release, which was shown by the increase in the frequency of miniature end-plate potentials and evoked muscle action potentials. These effects were not inhibited by a saturating concentration of LSD in either cell line. Adenylate cyclase activity was determined by a modification of the method of Salomon et al. (1974). A 5-hydro.xytryptamine-dependent increase in adenylate cyclase activity of 75-115% was observed in Hole-cell homogenates of the NCB-20 hybrid cells. The concentration of 5-hydroxytrptamine for halI:maximum activation (Kin' ) was 0.4-0.8 mcM and was unaffected by the addition of 50 mcM ascorbate or 100 mcM-pargyline to the reaction mixture. LSD produced a partial inhibition of the 5-hydroxytryptamine-dependent stimulation of adenylate cyclase (did = 10ns), and also produced a small
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