Summary
We investigated binding characteristics of [3H](+)-pentazocine in homogenates of post-mortem human frontal cortex. At equilibrium, specific binding was linear with protein concentration, was saturable, reversible, stereoselective, heat-labile and was nearly absent in the white matter. Saturation experiments revealed a K d of 3.68 ± 0.46nM and a Bmax of 0.636 ± 0.107 pmol/mg protein. The rank order of Ki values of competing substances was: haloperidol < N,N′-di(o-tolyl)guanidine (DTG) < (+)-SKF 10,047 < (—)-SKF 10,047. We also examined the influence of age, gender, hemisphere, post-mortem time and storage time of brain tissue at −80 °C on [3H](+)-pentazocine binding sites. Of these variables, only age was significantly related to [3]H](+)-pentazocine binding (diminished binding with increasing age). Together, our results demonstrate the presence of specific [3H](+)-pentazocine binding sites in post-mortem human brain tissue. Furthermore, the binding sites decrease with increasing age and are apparently independent of gender, hemisphere, post-mortem time and storage time of brain tissue.
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References
Basile AS, Paul IA, Mirchevich A, Kuijpers G, De Costa B (1992) Modulation of (+)- [3H]pentazocine binding to guinea pig cerebellum by divalent cations. Mol Pharmacol 42: 882–889
Bowen WD, de Costa BR, Hellewell SB, Walker JM, Rice KC (1993) [3H]-(+)-Pentazocine: a potent and highly selective benzomorphan-based probe for sigma-1 receptors. Mol Neuropharmacol 3: 117–126
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254
Cagnotto A, Bastone A, Mennini T (1994) [3H](+)-Pentazocine binding to rat brain σ1 receptors. Eur J Pharmacol Mol Pharmacol Sect 266: 131–138
DeCosta BR, Bowen WD, Hellewell SB, Walker JM, Thurkauf A, Jacobson AE, Rice KC (1989) Synthesis and evaluation of optically pure [3H]-(+)pentazocine, a highly potent and selective radioligand for σ receptors. FEBS Lett 251: 53–58
DeHaven Hudkins DL, Fleissner LC, Ford Rice FY (1992) Characterization of the binding of [3H](+)-pentazocine to σ recognition sites in guinea pig brain. Eur J Pharmacol Mol Pharmacol Sect 227: 371–378
Jansen KLR, Faull RLM, Dragunow M, Leslie RA (1991) Autoradiographic distribution of sigma receptors in human neocortex, hippocampus, basal ganglia, cerebellum, pineal and pituitary glands. Brain Res 559: 172–177
Keats AS, Telford J (1964) Narcotic antagonists as analgetics. Clinical aspects. In: Gould RF (ed) Molecular modification in drug design. Advances in chemistry, series 45. American Chemical Society, Washington DC, pp 170–176
Kloog Y, Nadler V, Sokolovsky M (1988) Mode of binding of [3H]dibenzocy-cloalkenimine (MK-801) to the N-methyl-D-aspartate (NMDA) receptor and its therapeutic implication. FEBS Lett 230: 167–170
Kornhuber J, Retz W, Riederer P, Heinsen H, Fritze J (1988) Effect of antemortem and postmortem factors on [3H]glutamate binding in the human brain [Erratum: Neurosci Lett 97 (1989) 359]. Neurosci Lett 93: 312–317
Kornhuber J, Mack-Burkhardt F, Kornradi C, Fritze J, Riederer P (1989a) Effect of antemortem and postmortem factors on [3H]MK-801 binding in the human brain: transient elevation during early childhood. Life Sci 45: 745–749
Kornhuber J, Mack-Burkhardt F, Korhuber ME, Riederer P (1989b) [3H]MK-801 binding sites in post-mortem human frontal cortex. Eur J Pharmacol 162: 483–490
Kornhuber J, Schoppmeyer K, Riederer P (1993) Affinity of 1-aminoadamantanes for the σ binding site in post-mortem human frontal cortex. Neurosci Lett 163: 129–131
Largent BL, Wikström H, Snowman AM, Snyder SH (1988) Novel antipsychotic drugs share high affinity for σ receptors. Eur J Pharmacol 155: 345–347
McPherson GA (1983) A practical computer-based approach to the analysis of radioligand binding experiments. Comput Progr Biomed 17: 107–114
Munson PJ, Rodbard D (1980) LIGAND: a versatile computerized approach for the characterization of ligand-binding systems. Anal Biochem 107: 220–239
Quirion R, Bowen WD, Itzhak Y, Junien JL, Musacchio JM, Rothman RB, Su T-P, Tam SW, Taylor DP (1992) A proposal for the classification of sigma binding sites. Trends Pharmacol Sci 13: 85–86
Shibuya H, Mori H, Toru M (1992) Sigma receptors in schizophrenic cerebral cortices. Neurochem Res 17: 983–990
Tam SW, Zhang A-Z (1988) σ and PCP receptors in human frontal cortex membranes. Eur J Pharmacol 154: 343–344
Walker JM, Bowen WD, Walker FO, Matsumoto RR, De Costa B, Rice KC (1990) Sigma receptors: biology and function. Pharmacol Rev 42: 355–402
Weissman AD, Su TP, Hedreen JC, London ED (1988) Sigma receptors in post-mortem human brains. J Pharmacol Exp Ther 247: 29–33
Zabetian CP, Staley JK, Flynn DD, Mash DC (1994) [3H]-(+)-Pentazocine binding to sigma recognition sites in human cerebellum. Life Sci 55: 389–395
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Kornhuber, J., Schoppmeyer, K., Bendig, C. et al. Characterization of [3H]pentazocine binding sites in post-mortem human frontal cortex. J. Neural Transmission 103, 45–53 (1996). https://doi.org/10.1007/BF01292615
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DOI: https://doi.org/10.1007/BF01292615