Effects of adenosine and adenine nucleotides on synaptic transmission in the cerebral cortex

Abstract

Adenosine and the adenine nucleotides have a potent depressant action on cerebral cortical neurons, including identified corticospinal cells. Other purine and pyrimidine nucleotides were either weakly depressant (inosine and guanosine derivatives) or largely inactive (xanthine, cytidine, thymidine, uridine derivatives). The 5'-triphosphates and to a lesser extent the 5'-diphosphates of all the purine and pyrimidines tested had excitant actions on cortical neurons. Adenosine transport blockers and deaminase inhibitors depressed the firing of cortical neurons and potentiated the depressant actions of adenosine and the adenine nucleotides. Methylxanthines (theophylline, caffeine, and isobutylmethylxanthine) antagonized the depressant effects of adenosine and the adenine nucleotides and enhanced the spontaneous firing rate of cerebral cortical neurons. Intracellular recordings showed that adenosine 5'-monophosphate hyperpolarizes cerebral cortical neurons and suppresses spontaneous and evoked excitatory postsynaptic potentials in the absence of any pronounced alterations in membrane resistance or of the threshold for action potential generation. It is suggested that adenosine depresses spontaneous and evoked activity by inhibiting the release of transmitter from presynaptic nerve terminals. Furthermore, the depressant effects of potentiators and excitant effects of antagonists of adenosine on neuronal firing are consistent with the hypothesis that cortical neurons are subject to control by endogenously released purines.

Electrophysiological Studies in Healthy Subjects Involving Caffeine

“…Tel./Fax: +351 217805219; E-mail: mamedemg@mail.telepac.pt. of adenosine receptors, sparing muscle fiber glycogen reserve [1]; secondly, a positive direct effect on calcium release from the sarcoplasmic reticulum by ryanodine receptors activation, a phenomenon readily observed in situ muscle preparation but with a non-physiological level of caffeine [2]; thirdly, increasing excitatory neurotransmitter activity as a consequence of adenosine receptor antagonism [3].…”

“…Caffeine antagonizes adenosine receptors at physiological doses, causing increased excitatory neurotransmitter release and lower neuronal activation threshold [3]. The augmented excitability of the serotoninergic neurons in the raphe nuclei can influence lower motor neurons (LMN) as they receive input from descending raphe fibers [14].…”

Adenosine Can Mediate its Actions through Generation of Reactive Oxygen Species

“…Therefore, it is possible that the observed adenosine-induced oxidant-mediated increase in cerebral arterial diameter observed in this study could be a critically important response in that it may have the potential to promote tissue perfusion and enhance delivery of oxygen and nutrients to tissues with increased energy demand. Furthermore, as adenosine is a known endogenous regulator of cerebral blood flow in health (Phillis, 1989;Phillis et al, 1979), its capacity to generate O 2 À and H 2 O 2 could also be considered as a possible indicator of Pretreatment of the CAMCs with either DNP or gp91ds-tat, but not the scrambled peptide gp91-scramb-tat, significantly reduced the concentration of 2-OH-E + stimulated by adenosine or CGS-21680 (n = 4 separate experiments for each group, * denotes P < 0.05 compared with control level of 2-OH-E + to that after stimulation with adenosine or CGS-21680; ** and w represents significant difference from the adenosine or CGS-21680-induced increase in 2-OH-E + concentration (P < 0.05) after treatment with DNP and gp91ds-tat, respectively).…”

Potentiation of the depression by adenosine of rat cerebral cortical neurones by progestational agents

“…Progesterone also depressed single unit responses in the rat cerebral cortex (Komisaruk et al, 1967). In a study of male rat cerebral cortical synaptosomes, it became apparent that progesterone is a potent inhibitor of adenosine uptake with IC20 and IC50 values of 1.l x IO-8M and 7.5 x 10-7 M (Phillis et al, 1985 (Phillis et al, 1979;Phillis & Wu, 1981), presumably by enhancing the extracellular concentrations of adenosine. Uptake inhibitors, administered intracerebroventricularly, depress locomotor activity in mice in a caffeine-sensitive fashion .…”

“…Earlier studies have shown that most ofthese neurones can be identified as corticospinal cells (Phillis et al, 1979). Pregnenolone sulphate was tested on a number of antidromically identified corticospinal neurones.…”