Preservation of kappa 1 opioid receptor recognition site density and regulation by G-proteins in the temporal cortex of patients with Alzheimer's disease.
The pharmacological properties of the kappa 1 opioid receptor were investigated in human post-mortem temporal cortical membranes from control and Alzheimer's disease brains, using the kappa 1-selective radioligand [3H]U69593. [3H]U69593 bound to a single high affinity site population with no significant difference between control (Bmax 31 +/- 4.14 fmol/mg protein, KD 1.01 +/- 0.26 nM) and Alzheimer's disease brains (Bmax 37 +/- 4.63 fmol/mg protein, KD 0.86 +/- 0.08 nM). Competition studies with dynorphin B and alpha-neoendorphin gave flat inhibition curves with Hill coefficients of 0.31 +/- 0.04 and 0.49 +/- 0.09 in the control brains and 0.38 +/- 0.05 and 0.48 +/- 0.08 in the Alzheimer's disease brains, respectively. The pI50 values for dynorphin B and alpha-neoendorphin were 8.73 +/- 0.17 and 8.48 +/- 0.09, respectively, in the control brains and 9.30 +/- 0.22 and 8.70 +/- 0.15 in the Alzheimer's disease brains. The guanine nucleotide analogue Gpp(NH)p inhibited binding by ca. 70% in both the control and Alzheimer's disease brains, the residual binding being sensitive to NaCl in both cases. These results indicate that the pharmacological properties and the functional integrity of G-protein coupling of the kappa 1 receptor recognition site are preserved in Alzheimer's disease temporal cortex.
Garlind
A
A
Department of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Cowburn
R F
RF
Wiehager
B
B
Ravid
R
R
Winblad
B
B
Fowler
C J
CJ
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D000700:Analgesics / Q000494:pharmacology; D044482:Benzeneacetamides; D001665:Binding Sites; D002462:Cell Membrane; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa; D013702:Temporal Lobe / Q000473:pathology*
D000700:Analgesics; D044482:Benzeneacetamides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D019204:GTP-Binding Proteins; C045444:U 69593