ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: The hydrolysis of phosphoinositides (PI) elicited in cerebellar granule cell cultures by agonists of metabolotropic glutamate receptors, glutamate and quisqualate, was enhanced when the cells were pretreated with concanavalin A (Con-A). A similar effect was produced by wheat germ agglutinin, but not by several other lectins tested. Con-A produced a dose-dependent effect (EC50= 3 μM) and increased the efficacy but not the potency of the agonists. In contrast, Con-A failed to enhance PI hydrolysis evoked by N-methyl-D-aspartate, kainate, carbachol, the calcium ionophore A23187, or 50 mM K+. The Con-A stimulatory effect was prevented by simultaneous pretreatment with the agonists of ionotropic quisqualate receptors quisqualate, kainate, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, but not by the antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). CNQX, which did not inhibit quisqualate-stimulated PI hydrolysis in untreated cells, abolished the component of quisqualate response enhanced by Con-A pretreatment. The pretreatment with Con-A also increased the influx of 45Ca2+ in granule cells stimulated by quisqualate. This increase was inhibited by CNQX. Moreover, the potentiation of PI hydrolysis by Con-A, but not the response to quisqualate alone, was abolished in the absence of Ca2+ and Na+. Pretreatment of granule cells with pertussis toxin inhibited PI hydrolysis stimulated by the metabolotropic quisqualate receptor and the Con-A-potentiated response by the same percentage, but Ca2+ influx induced by quisqualate was not affected. Hence, Con-A appears to enhance PI hydrolysis by acting at the ionotropic quisqualate receptor which results in an enhanced Ca2+ influx and a subsequent activation of phospholipase C through a pertussis toxin-sensitive G protein. This may indicate the existence of a functional cooperativity between the metabolotropic and ionotropic quisqualate receptors.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1991.tb03474.x
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