Delta receptors supraspinal

Rady, J.J., A.E. Takemori, P.S. Portoghese, and J.M. Fujimoto, Supraspinal delta receptor subtype activity of heroin and 6-monoacetyhnorphine in Swiss Webster mice, Life Sci., 55(8), 603-609, 1994. 

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. 

Four principal opioid receptor subtypes, designated as mu, kappa, delta, and sigma, have been characterized [1,2]. A newer receptor classification system utilizes labels OPRj, OPR and OPR, which correspond to mu, kappa, and delta receptors respectively [1,3,8]. Mu receptors (OPR ) mediate supraspinal analgesia, as well as respiratory depression, nausea and vomiting, miosis and bowel hypomotil-ity. Mu receptors also mediate euphoria and physical and psychological dependence, and are responsible for the increased release of prolactin and growth hormone [1,2]. 

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]. 

Zhu Y, King MA, Schuller AGP, Nitsche JF, Reidl M, Elde RP, Unterwald E, Pasternak GW, Pintar JE. Retention of supraspinal delta-like analgesia and loss of morphine tolerance in opioid receptor knockout mice. Neuron 1999 24 243-252. 

Shook, J.E., Lemcke, P.K., Gehrig, C.A., Hruby, V.J., Burks, T.F. Antidiarrheal properties of supraspinal mu and delta and peripheral mu, delta and kappa opioid receptors inhibition of diarrhea without constipation, J. Pharmacol. Exp. Ther. 1989, 249, 83-90. 

Biochemical studies have shown in vitro and in vivo differential inhib-itory/stimulatory modulation of spinal and supraspinal CCK release by mu and delta opioid agonists. Thus, delta opioid agonists enhance the release of CCK, whereas stimulation of mu opioid receptors reduces its release [81,82], Moreover, it has been shown that activation of CCKi receptors potentiates the analgesic responses induced by mu opioid agonists or by endogenous enkephalins, protected from their catabolism by the dual inhibitor RB 101, while activation of CCK2 receptors reduces them [80]. 

SUPRASPINAL ANTINOCICEPTION MEDIATED BY DELTA OPIOID RECEPTOR AGONIST AND INTERACTION BETWEEN MU AND DELTA OPIOID RECEPTORS IN THE BRAIN... 

Endogenous opioid peptides (endorphins, dynor-phins, enkephalins), have been termed the brain s own morphine. Their discovery in 1972 explained why the brain has opioid receptors when there were no opioids in the body. These peptides attach to specific opioid receptors, mainly p (mu), 5 (delta) or K (kappa) located at several spinal and multiple supraspinal sites in the CNS. Opioid receptors are part of the family of G-protein-coupled receptors (see p. 91) and act to open potassium channels and prevent the opening of voltage-gated calcium channels which reduces neuronal excitability and inhibits the release of pain neurotransmitters, including substance P. 

Major and minor sites of action hydrocodone activates supraspinal and spinal opioid receptors. It has agonistic effects at mu, kappa, and delta subtypes and provides dose-dependent analgesia, euphoria, reduced GI motility, and respiratory depression. Its effects can be reversed by naloxone. 

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