Transmitters peptide

There are now many examples of novel peptide transmitter systems that have been identified through orphan receptor ligand screening and greatly impacted the basic understanding of human physiology. Prime examples for the discovery of novel transmitter with therapeutic implications are the neuropeptides orphaninFQ/... 

Synaptic vesicles are the organelles in axon terminals that store neurotransmitters and release them by exocytosis. There are two types, the large dense-core vesicles, diameter about 90 nm, that contain neuropeptides, and the small synaptic vesicles, diameter about 50nm, that contain non-peptide transmitters. About ten vesicles per synapse are docked to the plasma membrane and ready for release, the readily releasable pool . Many more vesicles per synapse are stored farther away from the plasma membrane, the resting pool . When needed, the latter vesicles may be recruited into the readily releasable pool. Neuronal depolarization and activation of voltage-sensitive Ca2+... 

Figure 12.1 A comparison of the production, release and fate of classical transmitters such as glutamate and the monoamines and a peptide. (Most neurons use both classical and peptide transmitters)...

The opioid receptors are for the endogenous opioids, peptide transmitters, jS-endorphin, endomorphins, enkephalins, dynorphins and nociceptin. Thus all the problems of drugs based on peptides need to be overcome in order for the roles of these... 

The importance of peptide transmitters in the modulation of sleep and wakefulness has become apparent in recent years. Previous work had focused on the role of monoamines in the circuitry that regulates the transitions between states of vigilance. Histaminergic neurons in the tuberomammillary nucleus are known to be key players in the activation of subcortical afferents during wakefulness (Wada et al, 1991). Activity of noradrenergic neurons in the locus coeruleus correlates with the state of vigilance (Jones, 1991). The role of serotonergic neurons in rapid eye movement (REM) sleep has also been established (Lydic et al., 1987 Monti Jantos, 1992 Fabre et al., 2000). 

Endocannabinoids are derived from lipids, making them different from classical and peptide transmitters in several important respects. The latter are stored in vesicles after their synthesis and released by exocytosis in response... 

Table 2.5. Similarities and differences between the peptide transmitters/...

Neuropeptide Y [NPY] is a 36-amino acid peptide. The function of NPY, one of the most abundant peptide transmitters of the mammalian brain, remains unclear because of a lack of specific receptor antagonists. NPY meets many of the criteria of a neurotransmitter itself. NPY is costored and interacts with several monoaminergic neurons within the CNS [Lundberg et al. 1982], for example, noradrenergic afferents from the nucleus solitary tract to the amygdala. Both somatostatin and NPY colocalize at GABA interneurons within the amygdala, neocortex, and striatum. NPY also selectively modulates N-methyl-D-aspartate-induced hippocampal activation (pyramidal neurons] via oreceptors [Debonnel et al. 1994]. 

The role of peptidergic neurons is not so clear. Capsaicin, the hot chile pepper chemical that evokes release of peptide transmitters from several types of sensory nerves, has been shown to reproduce some of the signs of bronchial hyperreactivity in animal and human experiments. These findings led to the proposal that sensitization of afferent nerve endings played a major role in chronic airway hyperreactivity. However, peptide transmitter antagonists have not been able to prevent bronchoconstriction in several models. Clearly, much remains to be learned about airway pharmacology. 

Morphine and other opioids act on reeeptors for p-endor-phin and the related enkephalins. P-Endorphin was found earlier than the other peptide transmitters beeause opioids were made available by nature they eould be used as probes to find the reeeptors, whieh eould then in turn be used to sereen brain extracts for substances that would dis-plaee opioids from their reeeptors. 

Peptide transmitters Many peptides have been identified in the CNS, and some meet most or all of the criteria for acceptance as neurotransmitters. The best-defined ones are the opioid peptides (beta-endorphin, met- and leu-enkephalin, and dynorphin), which are distributed at all levels of the neuraxis. Some of the important therapeutic actions of opioid analgesics (eg, morphine) are mediated by receptors for these endogenous peptides. Substance P is localized in type C neurons involved in nociceptive sensory pathways in the spinal cord. Peptide transmitters differ from nonpeptide transmitters in that (1) the peptides are synthesized in the cell body and transported to the nerve ending via axonal transport, and (2) no reuptake or specific enzyme mechanisms have been identified for terminating their actions. 

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