Characterization and possible role of growth factor and lymphokine receptors in the regulation of cholinergic function in the mammalian brain.
Using in vitro receptor autoradiographic techniques, we characterized the distribution of various growth factor (GF) and lymphokine receptors in the rat brain. In neonatal brain, specific insulin-like GF-1 (IGF-1) and epidermal GF (EGF) sites were observed in various regions. In particular, dense [125I]IGF-1 and [125I]EGF labelling was seen in the hippocampal formation. In the adult (3-month old) rat brain, a broader distribution of IGF-1 sites was apparent, whereas few EGF sites were visualized. As in the neonate, the adult hippocampus was enriched with IGF-1 binding sites. In addition, high levels of interleukin-2 (IL-2) binding sites were detected in the hippocampus of the adult rat. Exogenous IGF-1, EGF, and IL-2 significantly reduced the potassium (25 mM)-evoked release of acetylcholine (ACh) from slices of rat hippocampus. The GF effects were restricted to the adult hippocampus; neither IGF-1 nor EGF altered ACh release from slices of immature (6- and 18-day old) rat brain. Moreover, the GF and IL-2-mediated effects on ACh release appear to be specific to the hippocampus. For example, ACh release from frontal cortex or striatum was not significantly affected by either GFs or IL-2. In summary, our results suggest that in the rat hippocampus, IGF-1, EGF, and IL-2 may be important modulators of cholinergic activity.
Araujo
D M
DM
Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada.
Lapchak
P A
PA
Chabot
J G
JG
Nair
N P
NP
Quirion
R
R
D000818:Animals; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism*
D007376:Interleukin-2; D011950:Receptors, Cholinergic; D013002:Somatomedins; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I