Regulation of hippocampal glutamate receptors: evidence for the involvement of a calcium-activated protease.

Publisher Website
Google Scholar
Abstract
Specific [3H]Glu binding to rat hippocampal membranes and the Ca-induced increase in this binding are markedly temperature-sensitive and are inhibited by alkylating or reducing agents as well as by various protease inhibitors. N-Ethylmaleimide, chloromethyl ketone derivatives of Lys and Phe, and tosylarginine methyl ester decrease the maximum number of [3H]Glu binding sites without changing their affinity for Glu. Preincubation of the membranes with Glu does not protect the Glu receptors from the suppressive effects of these agents. The proteases trypsin and .alpha.-chymotrypsin increase the maximum number of [3H]Glu binding sites. The effects of Ca on Glu binding are different across brain regions. Cerebellar membranes are almost insensitive, whereas hippocampal and striatal membranes exhibit a strong increase in the number of binding sites after exposure to even low concentrations of Ca. Apparently, an endogenous membrane-associated thiol protease regulates the number of [3H]Glu binding sites in hippocampal membranes and this is the mechanism by which Ca stimulates Glu binding. The possibility is discussed that the postulated mechanisms participate in synaptic physiology and, in particular, may be related to the long-term protentiation of transmission found in hippocampus under certain conditions.