Spinal cord opiate receptors

The plant alkaloids mimic the endogenous peptides enkephalins and endorphins (Chapter 12), which meditate nociception and sleep. There are three types of widely distributed opiate receptors. Mu receptors are concentrated in neocortex, striatum, thalamus, hippocampus, amygdala and spinal cord, delta receptors in neocortex and amydala, and kappa receptors in striatum, amygdala and hypothalamus (Mansour et al., 1988). 

The actions of all clinically used opiates can now be explained in terms of their acting as agonists at one of the four opiate receptors found in the brain, spinal cord and peripheral nervous system. All four receptors are inhibitory (Table 21.2). 

The opiate receptors in the spinal cord are predominantly of the mu and delta type and are found in the C-fibre terminal zone (the substantia gelatinosa) in the superficial dorsal horn. Considerable numbers of ORL-1 receptors are also found in this area. Up to 75% of the opiate receptors are found presynaptically on the C-fibre terminals and when activated inhibit neurotransmitter release. The opening of potassium channels will reduce calcium flux in the terminal and so there will be a resultant decrease in... 

Leysen, J.E., Gommeren, W., Niemegeers, C.J. [3H]Sufentanil, a superior ligand for mu-opiate receptors binding properties and regional distribution in rat brain and spinal cord, Eur. J. Pharmacol. 1983, 87, 209-225. 

Small quantities of opiate injected intrathecally or epidurally produce segmental analgesia. This observation led to the clinical use of spinal and epidural opiates during surgical procedures and for the relief of postoperative and chronic pain. As with local anesthesia, analgesia is confined to sensory nerves that enter the spinal cord dorsal horn in the vicinity of the injection. Presynaptic opioid receptors inhibit the release of substance P and other neurotransmitters from primary afferents, whereas postsynaptic opioid receptors decrease the activity of certain dorsal horn neurons in the spinothalamic tracts. 

The endorphins enkephalin and dynorphin possess natural analgesic (pain-relieving) qualities. When they bind to opiate receptors in the spinal cord, they suppress the ability of the brain to register pain. Heroin binds to these same opiate receptors in the brain and body. 

Miosis is a characteristic symptom of opiate administration, and while tolerance develops to many of the pharmacological effects of this class of drugs, tolerance to the miotic effects occurs at a much slower rate. Miosis is due to an excitatory action of the autonomic segment of the nucleus of the oculomotor nerve, an effect attributed to the stimulation of the mu receptors. In general, it would appear that the actions of morphine and its analogues on the brain, spinal cord and gastrointestinal tract are due to stimulation of the mu receptors. 

Previous work, which has not been revisited, showed that sulfatides are necessary for the optimal function of enzymes such as sodium-potassium-dependent ATPase, and the sulfatide content seems to be directly related to the activity of the enzyme (Karlsson et al., 1974). Sulfatides may also be involved in the functioning of certain opiate receptors (Craves et al., 1980) and in chloride transport systems (Zalc et al., 1978). Implantation in the spinal cord of a hybridoma secreting specific antisulfatide antibodies has been shown to cause demyelination of the CNS in the rat (Rosenbluth et al., 2003). Antisulfatide antibodies have been found in HIV... 

Kirby, M.L., Gale, T.F., and Mattio, T.G., Effects of prenatal capsaicin treatment on fetal spontaneous activity, opiate receptor binding, and acid phosphatase in the spinal cord, Exp. Neurol, 76,298-308, 1982. 

Endorphins. General term derived frrom endogenous (= originating from within) and morphine for analges-ically active peptides from the brain of mammals and man. The E. are biogenetically closely related to the enkephalins and dynorphins. Like these compounds, the E. block opiate receptors in the brain and spinal cord, thus preventing transmission of pain signals. The therapeutic use is hindered by the fact that they cannot pass the blood-brain barrier and, like synthetic opiates, cause addiction. 

LaMotte, C., Pert, C. B., and Snyder, S. H., 1976, Opiate receptor binding in primate spinal cord distribution and changes after dorsal root section. Brain Res. 112 407-412. 

Ninkovic, M., Hunt, S. P., and Kelly, J. S., 1981, Effect of dorsal rhizotomy on the autoradiographic distribution of opiate and neurotensin receptors and neurotensin-like immunoreactivity within the rat spinal cord. Brain Res., 230 111-119. 

Fig. 3. The autoradiographic localization of opiate receptors in the rat spinal cord. This is a bright-field micrograph showing regions of the dorsal horn. Note the high concentrations of autoradiographic grains (hence, opiate receptors) over the substantia gelatinosa (sg), while there is a much lower level over Lissauer s tract (LT) and an intermediate level over lamina IV. (Reproduced from Atweh and Kuhar 1977a.)...

There are many examples in which receptor distributions have been shown to complement neurotransmitter distributions dramatically. For example, it was shown that opiate receptors are highly concentrated in lamina I and II of the dorsal horn of the spinal cord (Atweh and Kuhar,... 

Atweh, S. F., and Kuhar, M. J., 1977a, Autoradiographic localization of opiate receptors in rat brain. I. Spinal cord and lower medulla. Brain Res. 124 53-68. 

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