Stimulatory neurotransmitters

Baclofen is a substituted analog of GABA. It is presumed that its action consists of a reaction with GABA receptors, which leads to an inhibition of stimulatory neurotransmitter release. 

Similar events occur at synapses where the presynaptic cell releases an inhibitory neurotransmitter such as y-aminobutyrate, except that here the receptor typically provides a pore that is specific for K+ or Cl" ions. K+ efflux or Cl " influx hyperpolarizes the plasma membrane to a potential more negative than the resting potential, opposing the depolarization induced by stimulatory neurotransmitters. 

We assume that acetylcholine is synthesized in compartment (I) by ChAT due to the activation reaction R in which the stimulatory neurotransmitter acetylcholine is synthesized ... 

Acetylcholine is destroyed (hydrolyzed) in compartment (II) by AchE in the degradation reaction R2 where the stimulatory neurotransmitter acetylcholine is degraded ... 

Nerve endings in the stomach secrete two stimulatory neurotransmitters acetylcholine and gastrin-releasing peptide. Their action is both direct on parietal cells and mediated through the secretion of gastrin from G cells and histamine from ECL cells. Gastrin acts on parietal cells directly and indirectly too, by stimulating the release of histamine. 

Acetylchoiine A stimulatory neurotransmitter in the central nervous system, which also controls mu.scles and sensory input signals. 

Several proteinogenic amino acids (see p. 60) have neurotransmitter effects. A particularly important one is glutamate, which acts as a stimulatory transmitter in the CNS. More than half of the synapses in the brain are glutaminergic. The metabolism of glutamate and that of the amine GABA synthesized from it (see below) are discussed in more detail on p.356. Glycine is an inhibitory neurotransmitter with effects in the spinal cord and in parts of the brain. 

Purine derivatives with neurotransmitter function are all derived from adenine-containing nucleotides or nucleosides. ATP is released along with acetylcholine and other transmitters, and among other functions it regulates the emission of transmitters from its synapse of origin. The stimulatory effect of caffeine is mainly based on the fact that it binds to adenosine receptors. 

Ionotropic receptors are ligand-gated ion channels (left half of the table). The receptors for stimulatory transmitters (indicated in the table by a ) mediate the inflow of cations (mainly Na""). When these open after binding of the transmitter, local depolarization of the postsynaptic membrane occurs. By contrast, inhibitory neurotransmitters (GABA and glycine) allow cr to flow in. This increases the membrane s negative resting potential and hinders the action of stimulatory transmitters hyperpolarization, 0). 

Long-term cocaine or amphetamine abuse leads to a deterioration of the nervous system. The body recognizes the excessive stimulatory actions produced by these drugs. To deal with the overstimulation, the body creates more depressant receptor sites for neurotransmitters that inhibit nerve transmission. A tolerance for the drugs therefore develops. Then, to receive the same stimulatory effect, the abuser is forced to increase the dose, which induces the body to create even more depressant receptor sites. The end result over the long term is that the abusers natural levels of dopamine and norepinephrine are insufficient to compensate for the excessive number of depressant sites. Lasting personality changes are thus often observed. 

Additional classification schemes will not be discussed here in any detail but include those with related gene and/or chromosome localizations and those with the same effector systems, (e.g., stimulatory or inhibitory G proteins or sodium, potassium, chloride, or calcium channels). These features of different receptors will be discussed as specific neurotransmitter receptors are mentioned throughout the rest of the book. 

Fluoroaluminate complexes can mimic the action of many hormones, neurotransmitters, and growth factors. G-protein-mediated cell responses are key steps in neurotransmission and intercellular signaling in the brain [20], and TFA acts as an active stimulatory species [21]. Exposure of osteoblasts to TFA results in a marked potentiation of intracellular orthophosphate transport, alluding to the anion s ability to increase bone mineralization [22]. Brief exposure to aluminum fluoride complexes induces prolonged enhancement of synaptic transmission [23] and can potentially affect the activity of many other ion channels and enzymes in the kidney [24]. Rapid and dynamic changes of the cytoskeletal actin network are of vital importance to the motility of many cells, and TFA induction effects a pronounced and sustained... 

Also important in understanding the function of the nervous system are the one-way flow of information across synapses and stimulatory versus inhibitory impulses Most synapses in the CNS will conduct an impulse (usually via a neurotransmitter) in one direction only that is, from the axon of the presynaptic neuron to the dendrite or cell body (soma) of the postsynaptic neuron (see Figures 1.2 and 1.3). This unidirectionality is critical in preserving the integrity of the information flow in the CNS. A particular postsynaptic neuron will have anywhere from 10,000 to 200,000 terminals, or receptor sites, that interact with presynaptic neurons. These terminals are activated by neurotransmitters. Activating some terminals will cause the postsynaptic neuron to fire an impulse to its neighbor neurons. When other terminals are activated, the same postsynaptic neuron will be especially quiet and will not fire off any impulses. This concept of stimulation versus inhibition and inhibitory impulses from one neuron to another is key in our discussion of mental illness and its treatment. 

At micromolar concentrations opioids cause an increase in the cell membrane threshold, shortened action potentials, and inhibition of neurotransmitter release. At nanomolar concentrations opioid agonists are excitatory and prolong the action potential via the stimulatory G proteins, which act on the adenylate cyclase/cAMP system and on protein kinase A-dependent ion channels. Tolerance is proposed to be the result of an increase in the association of opioid receptors to stimulatory G proteins, to an activation of A-methyl-o-aspartate receptors via protein kinase C, and calmodulin-dependent increases in cytosolic calcium, resulting in cellular hyperexcitability. 

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