Intracellular mechanisms of glutaminergic and cholinergic signal transduction in the cerebral cortex

Abstract

A complex method was used to study the effects of acetylcholine and glutamine on the dynamics of calcium and polyphosphoinositide regulatory system activities over prolonged periods of time in the mammalian cerebral cortex, after exposure to these substances in baseline conditions and in conditions of developing adaptive responses. Adaptive responses were induced by transient hypoxia with oxymetacil as an antioxidant. Agonist stimulation of choline and glutamate receptors produced prolonged calcium and phosphoinositide responses in cortical structures; these had specific characteristics after exposure to glutamate and acetylcholine. During the development of adaptive responses, these changes underwent significant modifications. The functional importance of these effects is discussed.

Calcium Transients in the Model of Rapidly Induced Anoxic Tolerance in Rat Cortical Slices: Involvement of NMDA Receptors

“…In particular, we previously noticed that, in olfactory cortical slices, in vitro 2-min PA improves the recovery of evoked focal potentials and prevents an excessive increase in Ca b induced by 10-min TA [15,18]. Similar results concerning neuronal activity and dynamics of Ca b in cat brain cortex were also obtained in vivo [12,30]. Data from our previous in vitro and in vivo experiments strongly suggest that tolerance to anoxia induced by preconditioning might be promoted by increased neuronal excitation and by enhanced calcium-and phosphoinositide-mediated intracellular signalling [9].…”

“…Still, the former phenomenon might play a signalling role for the induction of long-lasting tolerance. There is evidence that the mechanism of rapid preconditioning is associated with increased excitability of neurons [10][11][12], activation of A1 adenosine receptors [13], moderate increase in intracellular free and bound Ca 2+ levels and activation of phosphoinositide hydrolysis [14,15], and activation of protein kinase C [16,17], to mention only some examples of signal-related rapid responses to short-term anoxia. Nevertheless, the data accumulated so far are incomplete and no postulation of any unitary mechanism of rapid anoxic preconditioning can yet be made.…”

Involvement of intracellular regulatory systems in the adaptive effects of transient anoxia in vitro

“…Transient anoxia has been shown to induce NMDA receptor-mediated long-term potentiation of synaptic transmission in rat hippocampus slices--this is a common form of adaptive reaction [17]. Reoxygenation following transient anoxia in the cerebral cortex in vitro has been shown to result in a phosphoinositide response to the application of glutamate, which is not seen in controls [9]. This is evidence that metabotropic glutamate receptors associated with the phosphoinositide regulatory system are also probably involved in adaptive reactions.…”