Kappa opioids

Compared with the rest of the brain, the hypothalamus is relatively rich in both leu-enkephalin and met-enkephalin, with moderate to high levels found in most regions containing diencephalic DA neurons (Zamir et al., 1985), however, there is no sexual 

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). 

Agonists and antagonists of delta opioid receptors do not alter PHDA neuronal activity (Manzanares et al., 1993). No information is available regarding the effects of delta opioid receptor activation or blockade on the activities of IHDA or PeVDA neurons in the rostral periventricular nucleus and medial preoptic nucleus. 

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Central and peripheral analgesic agents from kappa-opioid agonists 95E405. 

Anzini M, Canullo L, Braile C, et ah Synthesis, biological evaluation, and receptor docking simulations of 2-[(acylamino)ethyl]-1,4-benzodiazepines as kappa-opioid receptor agonists endowed with antinociceptive and antiamnesic activity. J Med Chem 46 3833-3864, 2003... 

Bohn LM, Belcheva MM, Coscia CJ (2000) p-opioid agonist inhibition of kappa-opioid receptor-stimulated extracellular signal-regulated kinase phosphorylation is dynamin-dependent in C6 glioma cells. J Neurochem 74 574-581... 

Chao CC, Gekker G, Hu S, Sheng WS, Shark KB, Bu DP, Archer S, Bidlack JM, Peterson PK (1996a) kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression. Proc Natl Acad Sci USA 93 8051-8056 Chao CC, Hu S, Peterson PK (1996b) Opiates, gUa, and neurotoxicity. Adv Exp Med Biol 402 29-33... 

Kim E, Clark AL, Kiss A, Hahn JW, Wesselschmidt R, Coscia CJ, Belcheva MM (2006) Mu and kappa opioids induce the differentiation of embryonic stem cells to neural progenitors. J Biol Chem 281 33749-33760... 

The mu, delta and kappa opioid receptors are coupled to G° and G proteins and the inhibitory actions of the opioids occur from the closing of calcium channels (in the case of the K receptor) and the opening of potassium channels (for /i, d and ORL-1). These actions result in either reductions in transmitter release or depression of neuronal excitability depending on the pre- or postsynaptic location of the receptors. Excitatory effects can also occur via indirect mechanisms such as disinhibition, which have been reported in the substantia gelatinosa and the hippocampus. Flere, the activation of opioid receptors on GABA neurons results in removal of GABA-mediated inhibition and so leads to facilitation. 

Preliminary data indicate that in the reserpinised rat or MPTP marmoset, the enkephalin agonist (SNC80) reduces PD-like symptoms without causing increased activity, i.e. no trend to dyskinesias. Enadoline, a dynorphin-like kappa opioid agonist also has similar effects in the same models. Whether it would be similar in humans remains to be seen. 

Maneuf, YP, Mitchell, IJ, Crossman, AR, Woodruff, GN and Brotchis, JM (1995) Functional implications of Kappa opioid receptor mediated modulation of glutamate transmission in the output regions of the basal ganglia in rodent and primate models. Brain Res. 683 102-108. 

Oj-adrenergic receptors 5-HTi serotonin receptors Mu, delta, and kappa opioid receptors Benzodiaepine receptors D-2 dopamine receptors... 

As Shown in table 2, a comparative dose of 10 n units of PCP-like activity inhibited 3H-PCP binding in rat brain membranes, but did not inhibit binding of 3 H - d i hydromorphi ne, 3H - D - a 1 a2 - D -1 eu5-enkephalin, 3H-ethylketocyclazocine, 3H-diazepam, or -neurotensin. These results indicate that the active material is specific and selective from PCP receptors, as binding to the mu, delta, and kappa opioid receptors was unaffected, as was binding to benzodiazepine and neurotensin receptors. 

Das, D., Rogers, J., and Michael-Titus, A.T., Comparative study of the effects of mu, delta and kappa opioid agonists on 3H-dopamine uptake in the rat striatum and nucleus accumbens, Neuropharmacology, 33, 221, 1994. 

Kappa-Opioid Receptor Drugs as Cocaine Pharmacotherapies.93... 

Shippenberg T., Heidbreder C. Kappa opioid receptor agonists prevent sensitization to the rewarding effects of cocaine. NIDA Res. Monogr. 153 456, 1994. 

Mash D.C., Staley J.K. D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims. Ann. N.Y. Acad. Sci. 877 507, 1999. 

Wollemann M., Benhye S., Simon J. The kappa-opioid receptor evidence for the different subtypes. Life Sci. 52 599, 1993. 

Quirion R., Pilapil C., Magnan J. Localization of kappa opioid receptor binding sites in human forebrain using [3H]U69,593 Comparison with [3H]bremazocine. Cell Mol. Neurobiol. 7 303, 1987. 

Staley J., Rothman R., Partilla J. et al. Cocaine upregulates kappa opioid receptors in human striatum. Natl. Inst. Drug Abuse Res. Monogr. 162 234, 1996. 

Collins S.L., Kunko P.M., Ladenheim B., Cadet J.L., Carroll F.I., Izenwasser S. Chronic cocaine increases kappa-opioid receptor density lack of effect by selective dopamine uptake inhibitors. Synapse. 45 153, 2002. 

Spangler R., Bo A., Zhou Y., Maggos C., Yuferov V., Kreek M. Regulation of kappa opioid receptor mRNA in the rat brain by binge pattern cocaine administration and correlation with preprodynorphin mRNA. Mol. Brain Res. 38 71, 1996. 

Rosin A., Lindholm S., Franck J., Georgieva J. Downregulation of kappa opioid receptor mRNA levels by chronic ethanol and repetitive cocaine in rat ventral tegmentum and nucleus accumbens. Neurosci. Lett. 275 1, 1999. 

Spealman R., Bergman J. Modulation of the discriminative stimulus effects of cocaine by mu and kappa opioids. J. Pharmacol. Exp. Ther. 261 607, 1992. 

Gbck S., Maisonneuve I., Raucci J., Archer S. Kappa opioid inhibition of morphine and cocaine self-administration in rats. Brain Res. 681 147, 1995. 

Heidbreder C., Goldberg S., Shippenberg T. The kappa-opioid receptor agonist U-69,593 attenuates cocaine-induced behavioral sensitization in the rat. Brain Res. 616 335, 1993. 

Mello N.K., Negus S.S. Effects of kappa opioid agonists on cocaine- and food-maintained responding by rhesus monkeys. J. Pharmacol. Exp. Ther. 286 812, 1998. 

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