Neurotransmitters peptide

The surrounding redness caused by the vasodilatation of local blood vessels in the skin (hyperaemia). Histamine released at the site of contact acts on sensory nerve endings in the skin. Impluses travel along the axon to other peripheral branches of the same neuron to cause release of vasodilataory peptide neurotransmitters from nerve endings serving a wider area of skin than the initial contact point. Impluses reaching the CNS are interpreted as itch and pain. 

Hi-receptors in the adrenal medulla stimulates the release of the two catecholamines noradrenaline and adrenaline as well as enkephalins. In the heart, histamine produces negative inotropic effects via Hr receptor stimulation, but these are normally masked by the positive effects of H2-receptor stimulation on heart rate and force of contraction. Histamine Hi-receptors are widely distributed in human brain and highest densities are found in neocortex, hippocampus, nucleus accumbens, thalamus and posterior hypothalamus where they predominantly excite neuronal activity. Histamine Hrreceptor stimulation can also activate peripheral sensory nerve endings leading to itching and a surrounding vasodilatation ( flare ) due to an axonal reflex and the consequent release of peptide neurotransmitters from collateral nerve endings. 

Substance P is a peptide neurotransmitter in the NK family whose preferred receptor is the NKj receptor. Substance P is believed to be the primary mediator of the delayed phase of CINV and one of two mediators of the acute phase of CINV. 

Other neurotransmitters are larger peptides, such as the enkephalins. These peptide neurotransmitters are synthesized in the cell body of the neuron, usually as part of larger polypeptides from which they are subsequently cleaved. Following synthesis, they are incorporated into secretory granules that bud off from the Golgi apparatus and are then transported down the axon to the terminals. 

L E. The principal neurotransmitter released from preganglionic nerve terminals in all autonomic ganglia is acetylcholine. It acts on the postganglionic cell body to activate a nicotinic-cholinergic receptor resulting in a fast EPSP. Dopamine or norepinephrine or both are the mediators released from SIF cells or intemeurons. Neuropeptide Y is a peptide neurotransmitter. Angiotensin and serotonin are modulatory mediators. These last three contribute to the late very slow EPSP. 

It should be kept in mind that a single synapse may operate with as many as four transmitters simultaneously, in any combination of amine and peptide, or even peptide and peptide, within the groupings shown. The peptide neurotransmitters are stored separately, always in large synaptic vesicles are synthesized in the cell body of the neuron and are transported to the synapse after post-translational processing by fast (ATP-driven) transport systems. Amine neurotransmitters are synthesized in the synapse and are stored in small or large vesicles. Different populations of the same type of neurons may differ in their content of cotransmitters. 

Peptide neurotransmitters present problems for the drug designer because they are too large. Gaseous neurotransmitters likewise present problems for the dmg designer, but... 

We have already discussed the co-occurrence of small amine and peptide neurotransmitters their release is normally Ca + dependent, and they operate through signal transmission. They are also capable of regulating each other s release and even the synthesis, clustering, and affinity of receptors. Neuroendocrine cells are capable of producing more than one peptide, and thus an amine-peptide as well as a peptide-peptide combination is possible. It is known, for instance, that the vagus nerve contains substance P, vasointestinal peptide, enkephalin, cholecystokinin, and somatostatin— peptides with a hybrid combination of neural and hormonal communication properties. 

Endorphins, dynorphins, and enkephalins are natural peptide neurotransmitters that activate the opioid... 

For many of the neuropeptides the receptors are known, and more recently non-peptidic, small-molecule antagonists have become available. Application of these antagonists will help to elucidate further the involvement of peptidic neurotransmitters within the nervous system, as well as their contribution to mental disturbances. It is also expected that some of the recently developed antagonists may become useful therapeutic agents. 

The enkephalins, a group of peptide neurotransmitters, are examples of physiological substances that block387a glyeosylation (of glyco-... 

Furthermore, there does not appear to be any significant reuptake pump for neuropeptides, so once they are released, they are not recaptured for subsequent reuse (Fig. 1—9). The action of peptides is terminated by catabolic peptidases, which cut the peptide neurotransmitter into inactive metabolites. 

FIGURE 1—9- Neurotransmitter synthesis in a neuropeptidergic neuron. Neurotransmitter synthesis occurs only in the cell body because the complex machinery for neuropeptide synthesis is not transported into the axon terminal. Synthesis of a specific neuropeptide begins with the transcription of the pre-propeptide gene in the cell nucleus into primary RNA, which can be rearranged or edited to create different versions of RNA, known as alternative splice variants or pre-propeptide RNA. Next, RNA is translated into a pre-propeptide, which enters the endoplasmic reticulum, where its peptide tail is clipped off by an enzyme called a signal peptidase to form the propeptide, the direct precursor of the neuropeptide neurotransmitter. Finally, the propeptide enters synaptic vesicles, where it is converted into the neuropeptide itself. Synaptic vesicles loaded with neuropeptide neurotransmitters are transported down to the axon terminals, where there is no reuptake pump for neuropeptides. The action of peptides is terminated by catabolic peptidases, which cut the peptide neurotransmitter into inactive metabolites. 

FIGURE 2—16. Gene products are various proteins with a wide spectrum of functions, including receptors, ion channels, peptide neurotransmitters, enzymes, neurotrophic factors, transcription factors, reuptake carriers, and many, many more. 

FIGURE 5—72. Neurokinin A and neurokinin 2 receptors, part 2. Shown here is the formation of NK-A from the gamma PPT-A protein. The beta and gamma PPT-A proteins are the grandparents of NK-A and are cut down to size just as described for substance P, eventually forming the peptide neurotransmitter NK-A. Neurokinin A specifically binds to the NK-2 receptor. As for substance P, there is a mismatch between this neurotransmitter and its receptor anatomically, suggesting the important role of nonsynaptic volume neurotransmission for NK-A as well. However, the anatomical distribution of NK-A is different from that of substance P, and the anatomical distribution of NK-2 receptors is different from that of NK-1 receptors. 

Substance P and the neurokinins. The substance P and neurokinin family of peptide neurotransmitters was extensively discussed in Chapter 5 (see Figs. 5—69 through... 

Stahl, S.M. (1999) Substance P and the neurokinins, part 2 Novel peptide neurotransmitters in psychopharmacology. Journal of Clinical Psychiatry 60(2), 11—IB. 

Neale J. H., Bzdega T., and Wroblewska B. (2000). N-Acetylaspartylglutamate the most abundant peptide neurotransmitter in the mammalian central nervous system. J. Neurochem. 75 443M52. 

Best studied, among these ligands, are the lipid derivatives anandamide (AEA) (Devane etal., 1992) and 2-arachidonoylglycerol (2-AG) (Mechoulam et al., 1995 Sugiura et al., 1995), which differ from classical and peptide neurotransmitters in... 

A Postsynaptic Dopamine Receptor Regulating the Release or Turnover of Peptide Neurotransmitters ... 

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