Preservation of Somatostatin Receptors Coupled to the Inhibition of Adenylate Cyclase in the Cortex and Hippocampus in Senile Dementia of the Alzheimer Type
The distribution and the density of 125I-Tyr0-DTrp8-somatostatin (125I-SRIF) binding sites were compared by quantitative radioautography in the hippocampi and entorhinal cortices from normal humans and patients with senile dementia of the Alzheimer type (SDAT). In SDAT, entorhinal cortex concentrations of choline acetyl transferase and SRIF were significantly decreased as compared to controls. The neuroanatomical distribution of I25I-SRIF binding sites was similar in control and SDAT hippocampus and entorhinal cortex, being high in molecular layers of the dentate gyrus and stratum oriens of the CA1 and deeper cortical layers (V-VI), intermediate in superficial (II—III) cortical layers and low in subiculum, hilus of the dentate gyrus and cortical layer I and IV. Competition curves with SMS 201995 to displace 125I-SRIF binding allowed to differentiate between high (SS-A)-and low (SS-B)-affinity somatostatin binding sites. In control brains, SS A (Kd A = 0.06 ± 0.02 nM) represented 23–33% of the binding while SS B (KdB = 23.5 ± 2.8 nM) accounted for 67–77% of total specific binding, depending on the regions. In dentate gyrus and CA1, the proportion of SS-A was significantly reduced in SDAT as compared to controls. The reduction did not reach significance in the entorhinal cortex, and inhibition of adenylate cyclase activity by SRIF was equivalent in SDAT and controls. It is concluded from these data that the number of SS-A decreases in SDAT hippocampus but that SS-B and negative coupling to adenylate cyclase are preserved.