Rat brain membranes possess two high-affinity binding sites for [3H]somatostatin.

This report described the first use of [4-3H-Phe6]somatostatin-14 to characterize binding sites on rat brain membranes for somatostatin-14. This ligand is superior to previously used iodinated analogues and is chemically and biologically identical to the natural ligand. Two high-affinity binding sites were found, from Scatchard analysis of competitive displacement experiments, with Kd SS1 = 0.41 and Kd SS2 = 22.9 nM. Specific binding was reversible, and kinetic analysis of the dissociation and association time-course gave an apparent Kd of 0.44 nM, in good agreement with the Kd of the higher-affinity site. Specific binding of the ligand was enriched in cerebral cortex and hippocampus, with intermediate levels in the striatum, hypothalamus and midbrain, and low levels in the pons/medulla and cerebellum. This ligand should prove to be valuable for elucidating the physiological and pharmacological significance of the two subtypes of somatostatin binding sites we have demonstrated.