Different ionic requirements for somatostatin receptor subpopulations in the brain

Two populations of brain somatostatin (SS) receptors, one with high affinity for the somatostatin octapeptide analogue SMS 201-995 (SS1 type) and one poorly sensitive to this analogue (SS2 type) have been characterised in regard to their ionic requirements using two radioligands, the iodinated Tyr3 derivative of the octapeptide SS analog SMS 201-995 and the iodinated [Tyr11]-SS. Specific binding of 125I-[Tyr11]-SS to rat cortex membrane homogenates can be increased by approximately 180% in presence of 5 mM Mg2+. The increase in number of binding sites seen by Mg2+ is not accompanied by a marked increase in affinity for SS but for SMS 201-995: the low affinity binding for SMS 201-995 seen in absence of Mg2+ is replaced in part by higher affinity binding in presence of these ions. SMS 201-995 sensitive SS1 receptor subpopulation measured with 125I-204-090, a specific ligand for SS1 subpopulation, is massively increased in presence of Mg2+. However, SMS 201-995 insensitive SS2 receptor population measured with 125I-[Tyr11]-SS in presence of excess SMS 201-995 is unchanged in presence of Mg2+. The Mg2+-dependency can also be observed with autoradiography for extra cortical, i.e. hippocampal, brain SS receptors. 120 mM Na+ does not affect the total brain SS receptor population, but reduces the specific binding of SS1 receptors and increases that of SS2 receptors. Therefore, the rat brain, in particular the cortex, possesses a SMS 201-995-sensitive, Mg2+-dependent SS receptor subpopulation (SS1) as well as a SMS 201-995-insensitive, Mg2+-independent SS population (SS2).