Endogenous opioid 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... 

Nicotinic cholinergic receptors are located on cells that release a wide variety of transmitters (see chapter by Barik and Wonnacott, in this volume), so that nicotine interacts with multiple neurochemical pathways. The roles of cholinergic, dopaminergic, and endogenous opioid systems in physical dependence and withdrawal have been most thoroughly studied and documented. Research on the role of other transmitters and neurochemical mechanisms is rather scattered. Overall, however, research with rodent models of physical dependence has provided a wealth of potential targets for experimental treatments to aid smoking cessation. 

The dorsal horn of the spinal cord contains many transmitters and receptors. Some of these include peptides, eg. substance P, somatostatin and neuropeptide Y excitatory amino acids, e.g. glutamate and aspartate inhibitory amino acids, e.g. y-aminobutyric acid (GABA) nitric oxide endogenous opioids adenosine and the monoamines, e.g. serotonin and noradrenaline. There is, therefore, diverse therapeutic potential for... 

For a growing number of neurotransmitters, direct neurotrophic actions have been reported (for a review see Schwartz, 1992 Schwartz and Tani-waki, 1994). These transmitters are serotonin, acetylcholine, norepinephrine, glutamate and endogenous opioid peptides. Some of these neurotrophic transmitters may also be produced by astrocytes. The family of neurotransmitters synthesized by astrocytes comprises y-aminobutyric acid, glutamate, proenkephalin, neuropeptide Y, somatostatin and others. Martin (1992) has coined the term gliotransmitter for such substances. The role of gliotransmission in development and function of the mature nervous system has not been firmly established yet. It can be anticipated, however, that neurotrophic activity of astroglia-derived transmit-... 

Animal and human clinical studies demonstrate that both endogenous and exogenous opioids can also produce opioid-mediated analgesia at sites outside the CNS. Pain associated with inflammation seems especially sensitive to these peripheral opioid actions. The identification of functional p receptors on the peripheral terminals of sensory neurons supports this hypothesis. Furthermore, activation of peripheral preceptors results in a decrease in sensory neuron activity and transmitter release. Peripheral administration of opioids, eg, into the knees of patients undergoing arthroscopic knee surgery, has shown some clinical benefit. If they can be developed, opioids selective for a peripheral site would be useful adjuncts in the treatment of inflammatory pain (see Ion Channels Novel Analgesics). Moreover, new peripherally acting dynorphins may provide a novel means to treat visceral pain. 

There are dozens of presynaptic receptors for endogenous peptides. This review will focus on receptors for four peptides or peptide families the opioid peptides, neuropeptide Y and related peptides, adrenocorticotropic hormone (corticotropin, ACTH), and the orexins. This choice is representative, since part of the receptors inhibit and part of them facilitate transmitter release moreover, the receptors under consideration are coupled to the major G proteins, namely Gl/(), Gs and Gq (Table 1). 

Inhibitory neurons in the spinal cord are activated by descending pathways from the brain. Here the transmitters are GABA and enkephalin. Enkephalin is one of the endogenous endorphins, which are natural opioids. Enkephalin reduces the release of substance... 

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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