Neurotransmitters specific type

There is ample precedent for a modulatory role of K channels in behavior. The K channel blocker, 4-AP, selectively blocks component T (Bartschat and Blaustein 1985a). prolongs nerve action potentials, and enhances neurotransmitter release (Llinas et al. 1975). In man, intoxication with this agent may lead to dissociative behavior, agitation, confusion, convulsions, and coma (Spyker et al. 1980). However, the behavioral aberrations induced by 4-AP differ qualitatively from those induced by PCP. This implies that block of various types of presynaptic K channels may modify behavior and mental activity however, the precise nature of the behavioral manifestations is likely to depend upon the specific type of K channel that is affected. 

Action potentials are the means whereby information is passed from one neuron to an adjacent neuron. The balance between the excitatory and inhibitory impulses determines how many action potentials will reach the axonal terminal and, by releasing a specific type of neurotransmitter from the terminal, influence the adjacent neuron. Thus, in summary, chemical information in the form of small neurotransmitter molecules released from axonal terminals is responsible for changing the membrane potential at the synaptic junctions which may occur on the dendrites or directly on the cell body. The action potential then passes down the axon to initiate the release... 

By now you have a sense of the interwoven roles of dopamine, norepinephrine, and acetylcholine in the control of movement, reward, mood, arousal, and learning and attention. By considering how various drugs manipulate these neurotransmitter systems within the brain, scientists have discovered some consistent patterns that allow us to make predictions about what to expect when specific types of drugs are taken. The same holds true for the neurotransmitter system mentioned several times in this chapter serotonin. What are the consequences of its manipulation in the brain Read on. 

The postsynaptic neuron receives the neurotransmitter when the neurotransmitter engages a receptor site on the neuron s cell membrane. Each type of neurotransmitter will react with one specific type of receptor site and no other, similar to a lock and key. But it would not do to just let neurotransmitters sit there in the synapse causing unending activity, so there are other components in presynaptic neurons that take the extra neurotransmitters in a particular area back into the cell (this is called reuptake). Sometimes the neurotransmitters that have been taken back are broken down in the presynaptic neuron (by enzymes, such as monoamine oxidase, or MAO), and then are recycled in the vesicles for later use. There are at least 40 different chemicals that have been shown to act as neurotransmitters some of the most common are listed in Table 1.1. 

Neurotransmitters affect receptors in two basic ways. Some bind to receptors which are said to have ionic effects. These receptors, when activated, operate to open tiny pores (ion-channels), allowing electrically charged particles (ions) to enter the nerve cell. When numerous ionic receptors are activated, this can result in either an excitation of the nerve cell (action potential) or, conversely, a calming of the nerve cell (hyperpolarization, which makes it less likely that the cell will fire). Excitation or inhibition depends on which specific type of channel is activated. This phenomenon is responsible for eliciting immediate and transient changes in neuronal excitability (for example, this occurs when a motor neuron is activated and there is corresponding activation of a muscle, or when sensory events are perceived). 

Opioid neurotransmitters in the brain are peptides that modulate pain perception and/or the reaction to perceived pain they include the enkephalins, endorphins, dynorphins, and neoendorphins. All exert their effects by binding to specific types of opiate receptors that are located in various parts of the CNS, but particularly in those regions... 

It is, however, pertinent to mention here that the effects of autonomic (sympathetic) nervous system activation and, therefore, the effects of sympathomimetic drugs are evaluated mostly by the specific type and ultimately the localization of the post synaptic receptor to which the released neurotransmitter or exogenous sympathomimetic binds finally. 

There are several dozen different types of enzymes that metabolize specific types of chemicals. For example, alcohol dehydrogenase is an enzyme that specifically metabolizes alcohol, and acetylcholinesterase is an enzyme that specifically metabolizes one of our neurotransmitters and is affected by organophosphorus insecticides (see the Selection of Toxic Endpoints section below). 

Elucidation of the stmctural requirements for dmg interaction at the recognition site is by the study of stmcture—activity relationships (SAR), in which, according to a specific biologic response, the effects of systematic molecular modification of a parent dmg stmcture are determined. Such studies have permitted the classification of discrete classes of pharmacological receptors. For example, the neurotransmitter acetylcholine acts at both peripheral and central receptors which are of at least three distinct types. The effects of acetylcholine are mimicked in smooth and cardiac muscles and secretory... 

Figure 1.8 Some basic neuronal systems. The three different brain areas shown (I, II and III) are hypothetical but could correspond to cortex, brainstem and cord while the neurons and pathways are intended to represent broad generalisations rather than recognisable tracts. A represents large neurons which have long axons that pass directly from one brain region to another, as in the cortico spinal or cortico striatal tracts. Such axons have a restricted influence often only synapsing on one or a few distal neurons. B are smaller inter or intrinsic neurons that have their cell bodies, axons and terminals in the same brain area. They can occur in any region and control (depress or sensitise) adjacent neurons. C are neurons that cluster in specific nuclei and although their axons can form distinct pathways their influence is a modulating one, often on numerous neurons rather than directly controlling activity, as with A . Each type of neuron and system uses neurotransmitters with properties that facilitate their role...

The neurotransmitters of the ANS and the circulating catecholamines bind to specific receptors on the cell membranes of effector tissue. Each receptor is coupled to a G protein also embedded within the plasma membrane. Receptor stimulation causes activation of the G protein and formation of an intracellular chemical, the second messenger. (The neurotransmitter molecule, which cannot enter the cell, is the first messenger.) The function of intracellular second messenger molecules is to elicit tissue-specific biochemical events within the cell that alter the cell s activity. In this way, a given neurotransmitter may stimulate the same type of receptor on two different types of tissue and cause two different responses due to the presence of different biochemical pathways within each tissue. 

The autonomic nervous system (ANS) modifies contractile activity of both types of smooth muscle. As discussed in Chapter 9, the ANS innervates the smooth muscle layer in a very diffuse manner, so neurotransmitter is released over a wide area of muscle. Typically, the effects of sympathetic and parasympathetic stimulation in a given tissue oppose each other one system enhances contractile activity while the other inhibits it. The specific effects (excitatory or inhibitory) that the two divisions of the ANS have on a given smooth muscle depend upon its location. 

Neurotransmitter transporters There are probably at least five types of transport protein specific for glutamate, acetylcholine, catecholamines, glycine/GABA and ATP. The type of transporter contributes to determining the transmitter specificity of a synapse. 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

In contrast, pertussis toxin catalyzes the ADP-ribosyl-ation of a specific cysteine residue in Gai) G(m and Gal [1]. Only a subunits bound to their Py subunits can undergo this modification. Pertussis-toxin-mediated ADP-ribosylation inactivates these a subunits such that they cannot exchange GTP for GDP in response to receptor activation (Fig. 19-1B). By this mechanism, pertussis toxin blocks the ability of neurotransmitters to inhibit adenylyl cyclase or to influence the gating of K+ and Ca2+ channels in target neurons. However, since G is not a substrate for pertussis toxin, the toxin may not be able to block neurotransmitter-mediated inhibition of adenylyl cyclase in all cases. The Gq and Gn 16 types of G protein a subunit are not known to undergo ADP-ribosylation. 

How do a wide variety of neurotransmitters and hormones produce tissue- and cell-specific biological responses, if many such responses are mediated by the same intracellular messengers, cAMP and cAMP-depen-dent protein kinase Specificity is achieved at two levels at the level of tissue-specific receptors for the neurotransmitter or hormone and at the level of tissue-specific substrate proteins for the protein kinase. Only tissues that possess specific receptors will respond to a certain neurotransmitter or hormone. Moreover, since all cells contain very similar catalytic subunits of protein kinase A (see Ch. 23), the nature of the proteins that are phosphor-ylated in a given tissue depends on the types and amounts of proteins expressed in that tissue and on their accessibility to the protein kinase. 

There are at least five different types of voltage-dependent Ca2+ channel molecules, differing in their gating kinetics, modes of Ca2+-inactivation and Ca2+-iregulation, and sensitivity to specific marine toxins [13] (see Ch. 6). The distinctions between the types of channel are of considerable interest because the different subtypes are believed to subserve different cellular functions. For example, the control of neurotransmitter release in peripheral sympathetic neurons appears to be under the predominant control of N-type calcium channels. 

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