Xth International Symposium on Choline@ Mechanisms 419

and therefore suggests that nAChRs mediating dopamine release

also contain these suhunits. The subunits still detectable following

6-OHDA-induced lesion may be expressed in non-dopaminergic

neurons such as GABAergic neurons and interneurons of the SN

and VTA. et-l, ct7 (expressed only in the SN), p2 and p3 subunits

may he expressed in the large population of CABAergic neurons

from the SN pars reticulata which is also sampled together with

the SN pars compacta in our experiments, or in GABAergic in-

terneurons present in both the SN and the VTA. However, we

cannot exclude the possibility that these subunits are also present

on dopaminergic neurons. Indeed. a recent study has demonstrated the probable presence of p2 subunit-containing nAChRs in such

neurons’.

The molecular nature of native nAChR\ involved in the mo-

dulation of dopaminergic neurotransmisaion remains controver-

Gall, 4-7.9

and is the object of considerable interest. particularly

in relation to the known addictive properties of nicotine’. How

ever, the large number of nAChR subunits expressed in the SN

and VTA and the lack of subtype-selective drugs have hampered

the characterization of nAChRs responsible for the effect of ni-

cotine on the dopaminergic system. Here, using the RT-PCR

methodology. WC have identified the different neuronal nicotinic

acetylcholinc receptor subunit mRNAs expressed selectively in

the dopaminergic neurons of the SN and VTA. Our data also pro-

vide direct evidence for the heterogeneity of nicolinic receptor

subtypes in dopaminergic neurons. The molecular characterization

of these receptors is an essential first step in understanding the

relative contribution of different nAChRs in the modulation of physiological processes taking place in midbrain dopaminergic

systems.

References

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of Acetylcholinesterase: The ESTHER database and server

A. Chatonnet”, T. Hotelier’, X. Cousin’

“lXffc!r~im mtion Cellu/urre cf Crorwm c’ turd “lJn,tP l~~fi~nnor~yue. INKA-Eh’X4M. 2. /~lrr< P \‘&a. .1406,0 Mmtpellier; Frmr P

ESTHER (for esterases, a/b hydrolase enzyme and relatives) is a The maintenance of the system relies on the accuracy of infor-.

database of sequences phylogenetically related to cholinesterases. mation and up-to-date entering of data. Authors are encouraged to

These sequences define a homogeneous group of enzymes (car- submit data. Example forms are available but any computer-readahlr

hoxylesterascs. lipases and hormone-sensitive lipases) sharing a files can he sent to us, as the conversion tools used to enter dat:t

similar structure of a central beta-sheet surrounded by alpha-he- can he adapted to many different formats. This is made poshihlc

lices (I 1. The purpose of ESTHER is to provide help with com- hy the simplicity of the format of entry of raw data in ACeDB.

paring structures and functions of members of the family. In this

respect the compilation of compound? acting as inhibitor suhs- References trates or reactivators of acetylcholinesterase is valuable to con-

pare kinetic data dispersed in the literature. This is a crucial point (1) Cousin X., Hoteller T., Glep K., Toutant J.-P. and A. Chatonnel

when therapeutic effects are sought as some of these compounds (1998) aCHEdb: The database system tar ESTHER, the sib fold

can act as inhibitors and alow substrates for cholineserase (Bam- falnily of proteins and thz Cholinesterase gerlc server. Nuclrlc Acids Res 26 226-228.

buterol). or act as agonists of acetylcholine receptors and hind

acetylcholineqterase as well (Gallamine/flaxedil), or may interfere

with choline reuptake and acetylcholine synthesis. Information on

kinetic parameters of natural mutants of human hutyrylcholines-

terase is of utmost importance for monitoring pharmacokinetics

(2, A Chatonnat. T Hotelier. and X Cousin (1998) Kinetic para- meters of cholinesterasea interactmns with organophosphate\ retrieval and comparison tool> abailable through ESTHER da- tab;lsr Blol-Chem lnteracl. in press.

(3) Durbin R .md Thlerry-Mieg J., (lY9I).A C. elegans Database. Documenlatmn. code irnd data avadable tram anonymous F;TP

of such compounds (2). The database is available through the

Internet at: http://www.ensam.inra.fr/cholinesterase. The Database

\ervrrh dt lirmm lirmnl.fr, cele.mrc-lmb.cam.ac.uk and ncbi “lmmh.gov.

Managing System is ACeDB, initially developed for the C. &grm.s

genome project (3). Information about this system is available at

(4) Matthew\ D.E. and Shermnn B.K.. (1996~. ACEDB Gencrrnc Database Software FAQ, ftp:llrtfm.mit.edulpubius~- netlnz~s.an\wera/acedb-faq. http:/lprobe.“alusda.gov:8OOO/~c~~

the USDA server (4). Short tutorials fur searching the ESTHER

database and building tables have been published (2, 5). Here we

present examples of raw data as entered in ESTHER. Knowledge

of the different tags or fields available helps formulating queries

and building tables.

doc&cedbfaq.html,

(5) Chatonnet .A., Hotelier T. and Cousl” X. (1998) ESTHER (199X), aCHEdb a short tutorial. in B.P. Doctor, D.M. Quinn. R. L. Rotundo. and P. Taylor (Eds.), Structure and Function <it Cholinestrrarrs imd Related Proteins, Plenum, yew York, m plW\.