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Vol. 53, Issue 3, 392-401, March 1998
4,
2, and
5 Gene
Products
Department of Biology, University of California, San Diego, San
Diego, California 92093-0357
Increasing evidence suggests nicotinic receptors regulate developmental
events in the nervous system. We used [3H]epibatidine and
125I-
-bungarotoxin, together with subunit-specific
monoclonal antibodies, to distinguish and quantify nicotinic receptor
subtypes in developing chick brain. The results show that more than
three fourths of the epibatidine-binding receptors at both early and
late embryonic stages contain
4 and
2 subunits, representing
receptors previously distinguished by high affinity nicotine binding. A
fraction of these also contain the
5 gene product, which is
consistent with studies on transfected cells showing that the
4,
2, and
5 gene products coassemble to produce epibatidine-binding
receptors. A small portion of the receptors contain
3 and
4
subunits, assembled in part with either
4 or
2 subunits. The most
abundant nicotinic receptors, however, at both early and late embryonic
stages are those having high affinity for
-bungarotoxin rather than
epibatidine. Most contain
7 subunits, whereas about half contain
8 subunits as well. The sharpest developmental increase between
embryonic days 8 and 17/18 occurs with receptors containing
5
subunits, whereas receptors containing
3 or
4 subunits undergo no
specific increase. The three major receptor species (containing
4
and
2 but not
5 subunits;
7 subunits; or
7 and
8
subunits) each increase
3-fold during the same period. The results
indicate greater receptor complexity than appreciated previously; they provide information about the rules governing subunit assembly in
neuronal nicotinic receptors and draw attention to the role of
5
subunits in late development.
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