Neuronal receptors activation

Leukotrienes and Prostanoids. Arachidonic acid (AA) (213) and its metabohtes are iavolved ia cellular regulatory processes ia all three principal chemical signaling systems endocrine (see Hormones), immune, and neuronal (62). FoUowiag receptor activation or iacreased iatraceUular... 

In addition, adenosine is implicated in sleep regulation. During periods of extended wakefulness, extracellular adenosine levels rise as a result of metabolic activity in the brain, and this increase promotes sleepiness. During sleep, adenosine levels fall. Caffeine promotes wakefulness by blocking the interaction of extracellular adenosine with its neuronal receptors. ... 

Antiepileptics Na+, Ca2+ channels GABA receptors l Na+currents l Ca2+ currents GABA receptor activity l Excitability of peripheral and central neurons l Release of excitatory neurotransmitters Sedation, dizziness, cognitive impairment, ataxia, hepatotoxicity, thrombocytopenia... 

There are numerous transmitter substances. They include the amino acids glutamate, GABA and glycine acetylcholine the monoamines dopamine, noradrenaline and serotonin the neuropeptides ATP and NO. Many neurones use not a single transmitter but two or even more, a phenomenon called cotransmission. Chemical synaptic transmission hence is diversified. The basic steps, however, are similar across all neurones, irrespective of their transmitter, with the exception of NO transmitter production and vesicular storage transmitter release postsynaptic receptor activation and transmitter inactivation. Figure 1 shows an overview. Nitrergic transmission, i.e. transmission by NO, differs from transmission by other transmitters and is not covered in this essay. 

As with many neurons (e.g. NA) there are presynaptic autoreceptors on the terminals of dopamine neurons whose activation attenuate DA release. Although most of these receptors appear to be of the D2 type, as found postsynaptically, D3 receptors are also found. It is possible that in addition to the short-term control of transmitter release they may also be linked directly to the control of the synthesising enzyme tyrosine hydroxylase. It seems that autoreceptors are more common on the terminals of nerves in the nigrostriatal (and possibly mesolimbic) than mesocortical pathway. 

In view of the known cellular actions of DA, such as increased K+ efflux and reduced Ca + currents associated with Dj receptor activation in cell lines, inhibition would be the expected response to DA, especially as cyclic AMP, which is increased by Dj receptor activation also inhibits striatal neurons. In fact although many DA synaptic effects are blocked by Dj antagonists like haloperidol, the role of Di receptors should not be overlooked. 

Impulse-evoked release of 5-HT, like that of noradrenaline, is subject to fine control by a system of autoreceptors, in particular 5-HTia receptors on the cell bodies of neurons in the Raphe nuclei and 5-HTib/id receptors on their terminals. Because these are all G /o protein-coupled receptors, their activation reduces the synthesis of cAMP so that 5-HTia agonists (or 5-HT itself) decrease neuronal excitability and the firing of Raphe neurons whereas activation of 5-HTib/id receptors seems to disrupt the molecular cascade that links the receptor with transmitter release (see Chapter 4). 

Figure 11.5 Chloride distribution and the GABAa response. The change in membrane voltage (Fm) that results from an increase in chloride conductance following activation of GABAa receptors is determined by the resting membrane potential and the chloride equilibrium potential (Fci)- (a) Immature neurons accumulate CF via NKCC, while mature neurons possess a Cl -extruding transporter (KCC2). (b) In immature neurons GABAa receptor activation leads to CF exit and membrane depolarisation while in mature neurons the principal response is CF entry and h5q)erpolarisation. This is the classic inhibitory postsynaptic potential (IPSP)...

Dumuis, A, Sebben, M, Haynes, L, Pin, JP and Bockaert, J (1988) NMDA receptors activate the arachidonic acid cascade system in striatal neurons. Nature 336 68-70. 

Low concentrations of solubilised jS-albumin inhibit ACh release in slices from rat hippocampus and cortex areas which show degeneration in AzD, but not in slices from the striatum which is unaffected. While not totally specific to ACh, since some inhibition of NA and DA and potentiation of glutamate release have been reported, this effect is achieved at concentrations of A/i below those generally neurotoxic. Since jS-amyloid can inhibit choline uptake it is also possible (see Auld, Kar and Quiron 1998) that in order to obtain sufficient choline for ACh synthesis and the continued function of cholinergic neurons, a breakdown of membrane phosphatidyl choline is required leading to cell death (so-called autocannibalism), /i-amyloid can also reduce the secondary effects of Mi receptor activation such as GTPase activity... 

Figure 21.5 Mechanisms of opioid analgesia at the spinal level. Action potentials in nociceptive afferent fibres invade the terminal and by opening calcium channels (L, N and P-type) cause the release of glutamate and peptides that further transmit pain subsequent to activation of their postsynaptic receptors. Presynaptic opioid receptor activation (mu- and delta-mediated effects have been most clearly shown) opens potassium channels which hyperpolarise the terminal, so reducing transmitter release and inhibiting the postsynaptic neuron...

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