Delta receptors spinal

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). 

All opioids produce their effect by activating one or more of the three types of receptors. Thus analgesia involves the activation of the mu receptors that are located mainly at supraspinal sites and kappa receptors in the spinal cord delta receptors may also be involved but their relative contribution is unclear. Nevertheless, the actions of the opioids on these receptors is complex, as there is evidence that the same substance may act as a full agonist, or as an antagonist at different sites within the brain. 

Riba P, Ben Y, Smith AP, Furst S, Lee NM (2002) Morphine tolerance in spinal cord is due to interaction between mu- and delta-receptors. J Pharmacol Exp Ther 300 265-272 Smith FL, Javed RR, Elzey MJ, Dewey WL (2003) The expression of a high level of morphine antinociceptive tolerance in mice involves both PKC and PKA. Brain Res 985 78-88... 

Morphine is a naturally occmring alkaloid from the opium poppy seed. Modern formulations employ synthetic morphine. Major and minor sites of morphine activity include spinal and supraspinal opioid receptors. Morphine binds to and activates mu, kappa and delta receptor subtypes. 

Tramadol is a dual-mechanism, central-acting analgesic. It interacts weakly with p opioid receptors and to a lesser extent at kappa and delta receptors. Interactions at these receptors provide weak opioid agonist properties. It also has effects on noradrenergic and serotonergic reuptake proteins and accentuates spinal and supraspinal monamine-based analgesia [5,6,7]. Tramadol s opioid and non-opioid sites of action appear to act additively to provide more effective pain relief. Of the two tramadol enantiomers, the (+) enantiomer acts as a p receptor agonist and as a 5-HT reuptake inhibitor, while the (-) enantiomer is a norepinephrine reuptake inhibitor [2,5]. 

Glaum SR, Miller RJ, Hammond DL (1994) Inhibitory actions of delta 1-, delta 2-, and mu-opioid receptor agonists on excitatory transmission in lamina II neurons of adult rat spinal cord. 

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... 

Figure 21.5 Mechanisms of opioid analgesia at the spinal level. Action potentials in nociceptive afferent fibres invade the terminal and by opening calcium channels (L, N and P-type) cause the release of glutamate and peptides that further transmit pain subsequent to activation of their postsynaptic receptors. Presynaptic opioid receptor activation (mu- and delta-mediated effects have been most clearly shown) opens potassium channels which hyperpolarise the terminal, so reducing transmitter release and inhibiting the postsynaptic neuron...

Arvidsson U, Dado R, Riedl M. Lee J, Law P, Loh HH, Elde R, Wessendorf W. Delta-opioid receptor immunoreactiv-ity distribution in brainstem and spinal cord, and relationship to biogenic amines and enkephalin. J Neurosci 1995 15 1215-1235. 

Pugh G Jr, Abood ME, Welch SP. (1995). Antisense oligodeoxynucleotides to the kappa-1 receptor block the antinociceptive effects of delta 9-THC in the spinal cord. Brain Res. 689(1) 157-58. 

Opioid receptors are found in the dorsal horn as well as in other areas throughout the spinal cord and brain. Three major classes of opioid receptors exist mu receptors (/r), kappa receptors (k) and delta... 

Delta and kappa receptors can also contribute to analgesia, particularly at spinal level. Although morphine also acts on kappa and delta sites but it is not clear that up to what level they contribute in its analgesic action. 

Zhao GM et al Profound spinal tolerance after repeated exposure to a highly selective mu-opioid peptide agonist Role of delta-opioid receptors. J Pharmacol Exp Ther 2002 302 188. [PMID 12065716]... 

Glatzer NR, Smith BN (2005) Modulation of synaptic transmission in the rat nucleus of the solitary tract by endomorphin-1. J Neurophysiol 93 2530-40 Glaum SR, Miller RJ, Hammond DL (1994) Inhibitory actions of delta 1-, delta 2-, and mu-opioid receptor agonists on excitatory transmission in lamina II neurons of adult rat spinal cord. J Neurosci 14 4965-71... 

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