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Molecular genetics approach to the nicotinic acetylcholine receptor (AchR)
Author(s) -
Giraudat J.,
DevillersThiery A.,
Klarsfeld A.,
Changeux J.P.
Publication year - 1985
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/0736-5748(85)90109-1
Subject(s) - human physiology , nobel laureate , philosophy , biology , linguistics , poetry , endocrinology
NOT RECEIVED 36 NEUROPEPTIDE DYNAMICS STUDIED WITH A cDNA PROBE: PHARMACOLOGICAL IMPLICATIONS. I. Mocchetti, J.P. Schwartz and E. Costa Brain neuropeptides participate in synaptic function either as primary transmitters or as cotransmitters. In order to define their participation in various pharmacological responses it is important to evaluate the changes in their dynamic state during the action of centrally active drugs. The availability of specific antibodies for neuropeptides has made it possible to measure the changes in neuropeptide content that occur at the level of the nerve terminal. However, since peptides are synthesized as high molecular weight precursors one cannot utilize labeled amino acid incorporation and changes in specific activity to assess biosynthetic rates because of inherent technical difficulties. With specific cDNA probes one can measure the mRNA for the neuropept ide precursor. A combination of RIA and hybridization yields an estimation of neurfpeptide turnover. Daily injections of haloperidol repeated for 3 weeks increase striatal met enkephalin (ME) content and produce an increase of striatal proenkephalin mRNA (PE mRNA). Selective lesion of the nigro-striatal dopamine system with 6-hydroxydopamine also produces an increase of PE mRNA and ME levels, suggesting that dopamine tonically inhibits enkephalinergic turnover in the striatum. Fenfluramine elevates the hypothalamic content of ME without changing PE mRNA levels, suggesting that it acts at the level of peptide utilization. We propose that this approach will allow us to estimate in vivo peptide turnover and thus study the effects of various pharmacological treatment on the dynamic state of peptides.