Neurotransmission inhibitory

Altered synaptic properties Numerous changes in the properties of inhibitory (GABAergic) and excitatory (glutamatergic) synapses have been reported. While the simple adage of an imbalance between inhibitory and excitatory neurotransmission in epilepsy is not generally applicable, some forms of inhibition are lost or impaired in epilepsy. Likewise, an increased function of glutamate receptors has been demonstrated in some brain areas. 

Purinergic System. Figure 2 Schematic of sympathetic cotransmission. ATP and NA released from small granular vesicles (SGV) act on P2X and a-i receptors on smooth muscle, respectively. ATP acting on inotropic P2X receptors evokes excitatory junction potentials (EJPs), increase in intracellular calcium ([Ca2+]j) and fast contraction while occupation of metabotropic ar-adrenoceptors leads to production of inositol triphosphate (IP3), increase in [Ca2+]j and slow contraction. Neuropeptide Y (NPY) stored in large granular vesicles (LGV) acts after release both as a prejunctional inhibitory modulator of release of ATP and NA and as a postjunctional modulatory potentiator of the actions of ATP and NA. Soluble nucleotidases are released from nerve varicosities, and are also present as ectonucleotidases. (Reproduced from Burnstock G (2007) Neurotransmission, neuromodulation cotransmission. In Squire LR (ed) New encyclopaedia of neuroscience. Elsevier, The Netherlands (In Press), with permission from Elsevier). 

Somatostatin acts on various organs, tissues and cells as neurotransmitter, paracrine/autocrine and endocrine regulator on cell secretion, smooth muscle contractility, nutrient absorption, cell growth and neurotransmission [1]. Some of its mainly inhibitory effects are listed in Table 1. Somatostatin mediates its function via a family of heptahelical G-protein-coupled receptors termed... 

Of course, while the identification of these distinct systems may be useful there are many neural pathways that would not fit easily into one of them. Thus some inhibitory pathways, such as that from the caudate nucleus to substantia nigra, utilising GABA, are not intrinsic neurons. The dopamine pathway from the substantia nigra to striatum may start from a small nucleus but unlike other monoamine pathways it shows little ramification beyond its influence on the striatum. The object of the above classification is not to fit all neural pathways and mechanisms into a restricted number of functional categories but again to demonstrate that there are different forms of neurotransmission. 

Under normal conditions, a balance generally exists between excitatory and inhibitory neurotransmission. Changes in this balance can occur both peripherally and centrally resulting in exaggerated responses and sensitization such as that observed in inflammatory, neuropathic, or functional chronic pain. Pain... 

Okada, Y. and Kuroda, Y., Inhibitory action of adenosine and adenosine analogs on neurotransmission in the olfactory cortex slice of guinea pig Structure-activity relationships, European Journal of Pharmacology, 61, 137, 1980. 

Dent, J.A., Davis, M.W. and Avery, L. (1997) Avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans. EMBOJournal 16, 5867-5879. 

Li+, at therapeutically relevant concentrations, is a potent inhibitor of norepinephrine-stimulated adenylate cyclase activity ex vivo in both rat [133] and human brain [134], and it inhibits norepinephrine-stimulated cAMP accumulation in Li+-treated patients. Li+ also inhibits dopamine-stimulated cAMP accumulation in rat brain [135]. These inhibitory effects of Li+ have been shown to be region specific within rat brain, a fact that has obvious significance for a therapeutic mechanism of action. It is interesting that other antimanic drugs may also have dampening effects on dopaminergic neurotransmission. 

Seizure initiation is likely caused by an imbalance between excitatory (e.g., glutamate, calcium, sodium, substance P, and neurokinin B) neurotransmission and inhibitory (y-aminobutyric acid, adenosine, potassium, neuropeptide Y, opioid peptides, and galanin) neurotransmission. 

Various ginseng species have been shown to have both stimulatory and inhibitory effects on the CNS, and may modulate neurotransmission. Ginsenosides, and in particular ginsenoside Rbi (5), Rgi (84), and Re (88), seem to play a major role in these effects (Attele et ah, 1999 Rausch et ah, 2006). 

So far attention has concentrated on the effects of lithium on excitatory transmitters. There is evidence that the drug can also facilitate inhibitory transmission, an effect that has been attributed to a desensitization of the pres)maptic gamma-aminobutyric acid (GABA) receptors, which results in an increase in the release of this inhibitory transmitter. The increased conversion of glutamate to GABA may also contribute to this process. Thus it would appear that lithium has a varied and complex action on central neurotransmission, the net result being a diminution in the activity of excitatory transmitters and an increase in GABAergic function. 

Pharmacology The proposed mechanism of action of methyidopa is probably due to the drug s metabolism to alpha-methyl norepinephrine, which lowers arterial pressure by the stimulation of central inhibitory -adrenergic receptors, false neurotransmission or reduction of plasma renin activity. 

Pharmacology Benzodiazepines appear to potentiate the effects of gamma-aminobutyrate (GABA) (ie, they facilitate inhibitory GABA neurotransmission) and other inhibitory transmitters by binding to specific benzodiazepine receptor sites. 

It therefore appears that inhibitory somatodendritic 5-HTia receptor function is reduced by GR activation, leading to an enhancement of 5-HT neurotransmission generally, while the effects of corticosteroids on postsynaptic receptor function depends on the level of circulating corticosteroid differentially activating MR or GR receptors. 

Fig. 2. Schematic drawing of the adrenergic neurotransmission. Dependent on the target organ, the postsynaptic, G-protein-coupled receptors are of the a -, 2- or /Sj-adrenoceptor subtype. A presynaptic 2-adrenoceptor acts as an inhibitory autoreceptor. The predominant elimination pathway of the transmitter noradrenaline (NA) is the neuronal re-uptake...

If the balance between excitatory and inhibitory activity is shifted pharmacologically in favour of GABAergic transmission, then anxiolysis, sedation, amnesia and ataxia arise. On the other hand, an attenuation of the GABAergic system results in arousal, anxiety, restlessness, insomnia, exaggerated reactivity and even seizures. These pharmacological manifestations point to the contribution of inhibitory neurotransmission to the pathophysiology of brain disorders. A GABAergic deficit is particularly apparent in anx-... 

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