Enkephalin neurons

Activation of the D2 receptors inhibits the GABA/enkephalin neurons of the indirect pathway, and possibly also the direct pathway. It appears that Dj receptors could play an excitatory role in the direct pathway. 

Le Moine C, Normand E, Guitteny AF, Fouque B, Teoule R, Bloch B (1990b) Dopamine receptor gene expression by enkephalin neurons in rat forebrain. Proc Natl Acad Sci USA 57 230-234. 

A variety of chemically-identified neurons within the ARC receive both indirect (extrinsic) and direct (intrinsic) enkephalinergic neuronal input (Magoul et al., 1993) suggesting a role for enkephalin in the neuroendocrine regulation of pituitary hormone secretion. Enkephalin-IR perikarya in the bed nucleus of the stria terminalis, medial preoptic nucleus, periventricular nucleus and dorsomedial nucleus all provide extrinsic input to the rostral ARC, whereas intrinsic enkephalin neurons connect the rostral and caudal portions of the ARC (Magoul et al., 1993). Enkephalin-IR neurons innervate TH-IR neurons (perikarya and dendrites) in the DM-ARC (but not in the VL-ARC), (5-endorphin neurons in the VL-ARC, and NPY neurons in the ventromedial ARC (Magoul et al., 1994). There are symmetrical synaptic connections between enkephalin axon terminals and POMC perikarya in the ARC (Zhang et al., 1987), and reciprocal synaptic associations with NPY neurons in the ventromedial ARC (Li et al., 1993). 

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. 

Yoshimura M, North RA (1983) Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature 305(5934) 529-530... 

Figure 15.9 Peptide modulation of striatal input to the globus pollidus. Enkephalin released from axon terminals of neurons of the indirect pathway (see Fig. 15.2 for details) is thought to inhibit GABA release from the same terminals so that feedback (auto) inhibition is reduced. This will free the neurons to inhibit the subthalamic nucleus (SThN) and its drive to GPint and SNr which in turn will have less inhibitory effect on cortico-thalamic traffic and possibly reduce akinesia. Dynorphin released from terminals of neurons of the direct pathway may also reduce glutamate release and excitation in the internal globus pallidus and further depress its inhibition of the cortico-thalamic pathway. High concentrations of these peptides may, however, result in dyskinesias. (See Henry and Brotchie 1996 and Maneuf et al. 1995)...

Lamina II is also known as the substantia gelatinosa (SG) and can be divided into two layers, the outer layer (IIo) and the inner layer (Ili). This layer is densely packed with small neurons and lacks myelinated axons. Neurons with cell bodies in Hi receive inputs from low-threshold mechanoreceptive primary afferents, while those in IIo respond to inputs from high-threshold and thermoreceptive afferents. The intrinsic cells which comprise the SG are predominantly stalk and islet cells. Stalk cells are found located in lamina IIo, particularly on the border of lamina I, and most of their axons have ramifications in lamina I although some also project to deeper layers. These cells are thought to predominantly relay excitatory transmission. Islet cells, on the other hand, are located in Hi and have been demonstrated to contain the inhibitory neurotransmitters, y-aminobutyric acid (GABA), glycine and enkephalins in their dendrites. Hence these cells have been proposed to be inhibitory interneurons. 

Delta receptors are relatively selective for two related penta-peptides, methionine enkephalin and leucine enkephalin (met- and leu-enkephalin), which were isolated from porcine brain (Hughes 1975). Both met- and leu-enkephalin inhibit electrically induced contractions of guinea pig ileum, an effect that mimics those effects seen with opioid drugs, and is naloxone reversible. The enkephalins are processed posttranslational ly from proenkephalin, and secreted from central and peripheral neurons and endocrine cells in the adrenal medulla. 

GABA is the predominant intrinsic transmitter of the basal ganglia. Inhibition and disinhibition are considered to be the most important modes of information transfer in the basal ganglia. Ninety-five percent of all neurons in the striatum are GABAergic medium spiny neurons. These neurons are the striatal output neurons. The medium spiny neurons which give rise to the direct pathway also contain substance P or dynorphin as a co-transmitter, while those striatal output neurons that give rise to the indirect pathway contain enkephalin as a co-transmitter. Most striatal interneurons, as well as neurons in GPe, GPi and SNr are also GABAergic. Because striatal and GPe... 

Neurotransmitten Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic deft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic add, substance P, enkephalins, endorphins, and serotonin. [EU]... 

The classic endogenous opioid peptides are derived from one of three families of precursors proopiomelanocortin (POMC), pro-dynorphin, and pro-enkephalin. Many active opioid peptides are derived from these three, but the best known are )S-endorphin, enkephalin, and dynorphin. POMC is produced by nuclei in the hypothalamus and medulla (Khachaturian et al. 1985 Watson et al. 1978 Bloom et al. 1978). Enkephalin and dynorphin neurons are distributed to all levels of the central nervous system (Hokfelt et al. 1977 Khachaturian et al. 1983 Sar et al. 1978 Khachaturian et al. 1985). 

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. 

A clue to possible treatments for pain was discovered in the 1970s when scientists found specialized receptor cells in neurons called opiate receptors. These receptors appeared to he well suited for accepting natural painkillers that occur in the body, such as the enkephalins and endorphins. Enkephalins and endorphins are naturally occurring painkillers similar in their action to opium, morphine, and codeine. 

Impulse traffic in the neo- and pa-leospinothalamic pathways is subject to modulation by descending projections that originate from the reticular formation and terminate at second-order neurons, at their synapses with first-order neurons, or at spinal segmental interneurons (descending antinociceptive system). This system can inhibit impulse transmission from first- to second-order neurons via release of opio-peptides (enkephalins) or monoamines (norepinephrine, serotonin). 

---