Muscarinic cholinergic and glutamatergic reciprocal regulation of expression of hippocampal cholinergic neurostimulating peptide precursor protein gene in rat hippocampus.

摘要

Hippocampal cholinergic neurostimulating peptide, an undecapeptide originally isolated from the hippocampus of young rats, enhances acetylcholine synthesis in rat medial septal nucleus in vitro. Hippocampal cholinergic neurostimulating peptide is derived from the N-terminal region of its 21-kmol.wt precursor protein. The highest expression of the hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA is in hippocampal pyramidal neurons. In an in vitro rat hippocampal slice, preparation in which electrical stimulation could be delivered to the Schaffer collateral-CA1 pyramidal cell synapse, semi-quantitative non-radioisotopic in situ hybridization, demonstrated that expression of the hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA is regulated by neuronal activity. Selective inhibition with pharmacological agents revealed that the constitutive hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA level can be up-regulated by D-(-)-2-amino-5-phosphono-valeric acid, and that activity-dependent transcription can be inhibited by tetrodotoxin, nifedipine, 6-cyano-7-nitroquinoxaline-2,3-dione, and scopolamine, but not by mecamylamine.These results indicate that septal cholinergic neurons and hippocampal glutamatergic neurons exert a reciprocal influence over the expression of hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA in the hippocampus, and that the activity-dependent and constitutive expressions of hippocampal cholinergic neurostimulating peptide precursor protein messenger RNA may be regulated by different routes, involving calcium influx via L-type Ca(2+) channels and N-methyl-D-aspartate receptors.