- Email: [email protected]
Non-cholinergic functions of AChE
42
9thMcctiugofthcESN
CLINICAL AND BASIC RESEARCH OSSERVATION IMPLICATE CHOLINESTERASES WITH CELL DIVISION ASNORUALITIES G. Ehrlich*, Y. Lapidot H. Zakutl, D. Patinkin*, D.Ginzbcrg*, Lifsonl**. F. Eckstein3 & H. Soreq* lDcpt.of Ob.Gyn.The Edith Wolfson Med. Holon Tel-Aviv Univ.Isracl*Dept. Ctr. of Jerusalem, Hebrew Univ. Biol.Chem. Israel, 3 Dept. of Chem., Max Planck Med.,Gottingen, Germany Inst. of Exp.
FASCICULIN AS NERVOUS SYSTEM F.Daja9 Neurochemistry Avda. Italia
A TOOL TO STUDY CENTRAL ACETYLCHOLINESTERASES
Div. IIBCE, 3318,Montevideo,Urupuay
Fasciculin shows a (FASJ unique inhibitory profile, independent of the traditional classification of AChEs.To further characterize pharmacologically this profile,FAS was injected in different brain regions and the enzyme inhibition as well as effects on different beheviors,assessed.
We have found abnormal expression and /or amplification of the Human Acctyl -and Butyrylcholinesterase(ACHE,BCHE) ovarian & hemopoietic genes in brain, FAS inhibits AChEs of different brain cell preleukemic blood tumors, the regions in a similar way,not syndrome proliferation polycyfhtm.+. affecting other neurotransmitters severe thrombocytopenia the vcra & like dopamine in the striatum and the autoimmune due to the disease ?.!.!p_ti~ substantia nigra but increasing +r~t.hcmafosus. noradrenaline levels in the locus were further AS - oligonucleotides coeruleus.SO% inhibition of AChE in with BCHEmRNA employed to interfere the septum does not affect different as shown by RNA-PCR. This expression, learning tests in rodents. treatment diverted hemocytopoiesis in culturt,demonstrating the efficacy of AS-oligos as a research tool to study cell division involvement in CHEs explaining abnormalities, & possibly the aberrations in the above patients.
NON-CHOLINERGIC
FUNCTIONS
OF
AChE
University Department of S.A. Greenfield, Pharmacology, Mansfield Road, Oxford OX1 3QT
In various
brain regions there are large amOUntS acetvlcholinesterase relative tcl of (AChEI dispropor;ionately low levels of acetylcholine and choline acetyltransferase: one such region is the substsntia nigra. A soluble form of AChE is secreted
from the dendrites of dopaminergic nigrostriatal neurons, independent of cholinergic transmission. This dendritic secretion of AChE can be monitored 'online' by a system incorporating a chemiluminescent reaction. With this method it. is possible to show that both sensory and motor events can enhance secretion of AChE. The signals to the substantia finally triggering secretion originate nigra selectively from certain brain regions afferent to the substantia nigra (Raphe Nucleus, striatum), but not others (subthalamus). In turn, secreted AChE appears to facilitate movement for long periods of time. The cellular basis of this action is not at present fully understood. Nonetheless it appears that, independent of any enzymatic activity, AChE can activate ATPdependent potassium channels. This action could either be restricted to the membrane or reflect energy-consuming intracellular events. In any event secreted AChE clearly has a novel non-cholinergic 'modulatory' role in the eventual control of movement.
~~,,~~~
SNp and
FAS 88%
inhibits 31Xof the of the membrane-bound
AChE.
CELL LINEAGE CORTEX.
IN
THE
RAT
CEREBRAL
Jack Price, The National Institute for Medical Research, Mill Hill, London, NW7
lAA,
UK.
In this laboratory, we have been studying cell lineage in the cerebral cortex of the rat using the retroviral labelling technique. This method allows the germinal cells of the ventricular zone to be labelled, such that their fate and that of their progeny can be followed. We have discovered that most embryonic precursors in the cortex are restricted: they generate a single cell type. Thus fibrous astrocytes, protoplasmic astrocytes, and oligodendrocytes, each have a dedicated population of precursor cells. Interestingly, the major exception to this rule is a population of precursor cells that generate both neurones and oligodendrocytes. I shall discuss the evidence for these different precursor cell types, and consider how they may be derived during embryonic development.
9thMcctiugofthcESN
CLINICAL AND BASIC RESEARCH OSSERVATION IMPLICATE CHOLINESTERASES WITH CELL DIVISION ASNORUALITIES G. Ehrlich*, Y. Lapidot H. Zakutl, D. Patinkin*, D.Ginzbcrg*, Lifsonl**. F. Eckstein3 & H. Soreq* lDcpt.of Ob.Gyn.The Edith Wolfson Med. Holon Tel-Aviv Univ.Isracl*Dept. Ctr. of Jerusalem, Hebrew Univ. Biol.Chem. Israel, 3 Dept. of Chem., Max Planck Med.,Gottingen, Germany Inst. of Exp.
FASCICULIN AS NERVOUS SYSTEM F.Daja9 Neurochemistry Avda. Italia
A TOOL TO STUDY CENTRAL ACETYLCHOLINESTERASES
Div. IIBCE, 3318,Montevideo,Urupuay
Fasciculin shows a (FASJ unique inhibitory profile, independent of the traditional classification of AChEs.To further characterize pharmacologically this profile,FAS was injected in different brain regions and the enzyme inhibition as well as effects on different beheviors,assessed.
We have found abnormal expression and /or amplification of the Human Acctyl -and Butyrylcholinesterase(ACHE,BCHE) ovarian & hemopoietic genes in brain, FAS inhibits AChEs of different brain cell preleukemic blood tumors, the regions in a similar way,not syndrome proliferation polycyfhtm.+. affecting other neurotransmitters severe thrombocytopenia the vcra & like dopamine in the striatum and the autoimmune due to the disease ?.!.!p_ti~ substantia nigra but increasing +r~t.hcmafosus. noradrenaline levels in the locus were further AS - oligonucleotides coeruleus.SO% inhibition of AChE in with BCHEmRNA employed to interfere the septum does not affect different as shown by RNA-PCR. This expression, learning tests in rodents. treatment diverted hemocytopoiesis in culturt,demonstrating the efficacy of AS-oligos as a research tool to study cell division involvement in CHEs explaining abnormalities, & possibly the aberrations in the above patients.
NON-CHOLINERGIC
FUNCTIONS
OF
AChE
University Department of S.A. Greenfield, Pharmacology, Mansfield Road, Oxford OX1 3QT
In various
brain regions there are large amOUntS acetvlcholinesterase relative tcl of (AChEI dispropor;ionately low levels of acetylcholine and choline acetyltransferase: one such region is the substsntia nigra. A soluble form of AChE is secreted
from the dendrites of dopaminergic nigrostriatal neurons, independent of cholinergic transmission. This dendritic secretion of AChE can be monitored 'online' by a system incorporating a chemiluminescent reaction. With this method it. is possible to show that both sensory and motor events can enhance secretion of AChE. The signals to the substantia finally triggering secretion originate nigra selectively from certain brain regions afferent to the substantia nigra (Raphe Nucleus, striatum), but not others (subthalamus). In turn, secreted AChE appears to facilitate movement for long periods of time. The cellular basis of this action is not at present fully understood. Nonetheless it appears that, independent of any enzymatic activity, AChE can activate ATPdependent potassium channels. This action could either be restricted to the membrane or reflect energy-consuming intracellular events. In any event secreted AChE clearly has a novel non-cholinergic 'modulatory' role in the eventual control of movement.
~~,,~~~
SNp and
FAS 88%
inhibits 31Xof the of the membrane-bound
AChE.
CELL LINEAGE CORTEX.
IN
THE
RAT
CEREBRAL
Jack Price, The National Institute for Medical Research, Mill Hill, London, NW7
lAA,
UK.
In this laboratory, we have been studying cell lineage in the cerebral cortex of the rat using the retroviral labelling technique. This method allows the germinal cells of the ventricular zone to be labelled, such that their fate and that of their progeny can be followed. We have discovered that most embryonic precursors in the cortex are restricted: they generate a single cell type. Thus fibrous astrocytes, protoplasmic astrocytes, and oligodendrocytes, each have a dedicated population of precursor cells. Interestingly, the major exception to this rule is a population of precursor cells that generate both neurones and oligodendrocytes. I shall discuss the evidence for these different precursor cell types, and consider how they may be derived during embryonic development.