Regional distribution of somatostatin receptor binding and modulation of adenylyl cyclase activity in Alzheimer's disease brain.
We have previously reported a reduction in the inhibitory effect of somatostatin on adenylyl cyclase activity in the superior temporal cortex of a group of Alzheimer's disease cases, compared to a group of matched controls. In the present study, the levels of high affinity 125I-Tyr11-somatostatin-14 binding, its modulation by guanine nucleotides and the effects of somatostatin on adenylyl cyclase activity have been measured in preparations of frontal cortex, hippocampus, caudate nucleus and cerebellum from the same patient and control groups. A significant reduction in 125I-Tyr11-somatostatin-14 binding was observed in the frontal cortex, but not other regions, of the Alzheimer's disease group, compared with control values. The profiles of inhibition of specific 125I-Tyr11-somatostatin-14 binding by Gpp(NH)p were similar in all regions in both groups. No significant differences in basal, forskolin-stimulated, or somatostatin and neuropeptide Y inhibitions of adenylyl cyclase activity were found between the two groups. The pattern of change of somatostatin binding in the Alzheimer's disease cases observed in the present study differs from the reported pattern of loss of somatostatin neurons and may be secondary to the degeneration of somatostatin receptor-bearing cholinergic afferents arising from the nucleus basalis. The results of this study indicate that impaired somatostatin modulation of adenylyl cyclase is not a global phenomenon in Alzheimer's disease brain and also that there are no major disruptions of somatostatin receptor-G-protein coupling or of adenylyl cyclase catalytic activity in this disorder.
Alzheimer's Disease Research Group, Karolinska Institute, Department of Geriatric Medicine, Huddinge, Sweden.
L
L
Bergström
A
A
Garlind
L
L
Nilsson
I
I
Alafuzoff
C J
CJ
Fowler
B
B
Winblad
R F
RF
Cowburn
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D002525:Cerebellar Cortex / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009928:Organ Specificity; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D017481:Receptors, Somatostatin; D012016:Reference Values; D013004:Somatostatin / Q000378:metabolism*
D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D006165:Guanylyl Imidodiphosphate; D013004:Somatostatin; D000262:Adenylyl Cyclases