Excitatory amino acids inhibit stimulation of phosphatidylinositol metabolism by aminergic agonists in hippocampus

Abstract

Since the initial observations in the 1950s a large number of neurotransmitters and hormones have been shown to influence phosphatidylinositol (PI) metabolism in brain and peripheral ganglia (see ref. 3 for review). This has led to the suggestion that PI is part of an intracellular second messenger system for some types of diffusible chemical factors. Consistent with this are recent reports that one of the products of PI turnover (diacylglycerol) stimulates the Ca-dependent phospholipid-dependent protein kinase (kinase C) while a second (inositol trisphosphate) causes the release of calcium from intracellular stores. Thus it is possible that at least some brain neurotransmitters utilize the PI system to produce functional effects that are in addition to and which outlast the very brief physiological responses they elicit. Although it had been anticipated that another class of receptors might inhibit receptor-mediated stimulation of PI breakdown, no clear examples of such effects have been described. We now report that acidic amino acids, which are that acidic amino acids, which are thought to be excitatory neurotransmitters at the majority of brain synapses, strongly inhibit the stimulation of PI metabolism elicited by carbachol, histamine, or by potassium-induced depolarization, without changing the response to noradrenaline. As well as indicating a novel function for the excitatory amino acids, these results suggest that the central nervous system possesses cell-cell interactions of a previously unsuspected type.

Receptor Activation and Inositol Lipid Hydrolysis in Neural Tissues

“…Thus, although forskolin failed to reduce either carbamoylcholine-or norepinephrine-mediated stimulation of inositol lipid turnover in cerebral cortex slices (Hollingsworth and Daly, 1985), an inhibitory effect was observed by Nicchitta and Williamson (1986), using nerve ending preparations. Similarly, although it has been claimed that administration of excitatory amino acids (kainic acid, NMDA, or DL-homocysteate) exerts an inhibitory effect on phosphoinositide turnover elicited by carbamoylcholine, histamine, or K+ depolarization, and not by norepinephrine (Baudry et al, 1986), an inhibition of norepinephrinelinked, and not of carbamoylcholine-linked, stimulation was observed by Nicoletti et al (1986b).…”

“…Thus, although forskolin failed to reduce either carbamoylcholine-or norepinephrine-mediated stimulation of inositol lipid turnover in cerebral cortex slices (Hollingsworth and Daly, 1985), an inhibitory effect was observed by Nicchitta and Williamson (1986), using nerve ending preparations. Similarly, although it has been claimed that administration of excitatory amino acids (kainic acid, NMDA, or DL-homocysteate) exerts an inhibitory effect on phosphoinositide turnover elicited by carbamoylcholine, histamine, or K+ depolarization, and not by norepinephrine (Baudry et al, 1986), an inhibition of norepinephrinelinked, and not of carbamoylcholine-linked, stimulation was observed by Nicoletti et al (1986b).In the retina, light stimulation elicits an increased phosphoinositide turnover that is mediated in part by release of ACh (Anderson and Hollyfield, 198 I ;Anderson et al, 1983; Schmidt, 1983a,b) and can be blocked by administration of glycine (Anderson and Hollyfield, 1984). The inhibitory effect of glycine is, in turn, reversed by preincubation with strychnine.…”

Modulatory effects of NMDA on phosphoinositide responses evoked by the metabotropic glutamate receptor agonist 1S,3R‐ACPD in neonatal rat cerebral cortex

“…Thus, other groups have found that inhibitory effects of NMDA on agonist-stimulated phosphoinositide responses are essentially unaffected by removal of extracellular Ca2", whilst removal of Na' (with suitable substitution to maintain osmolarity and [C1-]) profoundly affected the modulatory effect of NMDA (Baudry et al, 1986;Morrisett et al, 1990). Although it is difficult to reconcile these conflicting results, it is noteworthy that the latter studies were both performed in hippocampal slices, whereas the former, which support a pre-eminent role for Ca2" in the neurotoxic action of NMDA, were all conducted in cerebral cortical or striatal preparations.…”

Stimulatory and inhibitory actions of excitatory amino acids on inositol phospholipid metabolism in rat cerebral cortex

“…In addition to these stimulatory effects, an inhibitory action of EAAs against agonist-stimulated inositol phospholipid breakdown has been observed in rat hippocampus (Baudry et al, 1986;Nicoletti et al, 1986a) and mouse striatal neurones (Schmidt et al, 1987).…”