Abstract:
:Insulin-like growth factor-I elicits a long-term depression of the glutamate-induced GABA release in the adult rat cerebellum that lasts at least several hours. We studied whether protein kinase C and nitric oxide may be involved in this effect of insulin-like growth factor-I on GABA release since both signalling pathways have been implicated in other forms of neuromodulation in the cerebellum. By using microdialysis in the adult rat cerebellum, we found that either an inhibitor of protein kinase C (staurosporine) or of nitric oxide synthase (Nw-nitro-L-arginine methyl ester) counteracted the long-term, but not the acute effects of insulin-like growth factor-I on glutamate-induced GABA release. On the contrary, when either an activator of protein kinase C (phorbol ester), or an nitric oxide donor (L-arginine), were given with glutamate, they mimicked only the acute effects of insulin-like growth factor-I on glutamate-induced GABA release. Finally, when both protein kinase C and nitric oxide-synthase were simultaneously inhibited by conjoint administration of staurosporine and Nw-nitro-L-arginine methyl ester, a complete blockage of both the short and the long-term effects of insulin-like growth factor-I on GABA release was obtained. These results, indicate that: (i) activation by insulin-like growth factor-I of either the protein kinase C or nitric oxide-signalling pathways is sufficient for the short-term inhibition of glutamate-induced GABA release; and (ii) simultaneous activation of both the protein kinase C and the nitric oxide signalling pathways is necessary for insulin-like growth factor-I to induce a long-term depression of GABA responses to glutamate. Thus, long-term depression of glutamate-induced GABA release by insulin-like growth factor-I in the cerebellum is mediated by simultaneous activation of both protein kinase C and nitric oxide-signalling pathways.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
Castro-Alamancos MA,Arevalo MA,Torres-Aleman Idoi
10.1016/0306-4522(95)00472-6subject
Has Abstractpub_date
1996-02-01 00:00:00pages
843-7issue
4eissn
0306-4522issn
1873-7544pii
0306-4522(95)00472-6journal_volume
70pub_type
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