[Cellular reactions after stimulation of receptors: research model for evaluation of effects and action mechanisms of drugs for discovery of innovative drugs].
When cellular stimulants such as neurotransmitters, hormones, autacoids, cytokines and growth factors stimulate their respective specific receptors in the plasma membranes of cells, a variety of responses are elicited. GTP-binding proteins are also involved in the reactions between receptors and cellular effectors. Stimulation of receptors are subsequently coupled to the activation of ion channels, turnover of inositol phospholipid metabolism, adenylate cyclase and guanylate cyclase, inhibition of adenylate cyclase and potentiation of all proliferation. Active substances such as the so-called second messengers are produced in the cells. In this article, two findings are described: 1) Ca2+, which increases by stimulation of receptors with neurotransmitters and hormones, stimulated Ca2+/calmodulin-dependent protein kinase II in cell systems such as NG108-15 neuroblastoma x glioma hybrid cells and primarily cultured neuronal cells of rat hippocampus. 2) Coupling preferences and possible transduction mechanisms from experiments on NG108-15 cells and NL308 neuroblastoma x fibroblast hybrid cells which have been stably transfected with DNA for m1, m2, m3 and m4 muscarinic acetylcholine receptors were examined. These results may provide a useful research model for examining and evaluating the effects and mechanisms of the drugs on a living system and may help develop useful methodology for the discovery of innovative drugs.
Miyamoto
E
E
Department of Pharmacology, Kumamoto University School of Medicine, Japan.
Higashida
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D015195:Drug Design; D019204:GTP-Binding Proteins / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism; D013268:Stimulation, Chemical
D016207:Cytokines; D006133:Growth Substances; D007473:Ion Channels; D018377:Neurotransmitter Agents; D011955:Receptors, Drug; D019204:GTP-Binding Proteins; D002118:Calcium