The new pharmacology of somatostatin and its multiple receptors.

A large number of somatostatin analogs taken from several major families of peptides has been examined for binding to three newly discovered somatostatin receptors (SSTR1, 2 and 3) transfected and expressed in various cell membrane preparations. Extremely potent octapeptide analogs related to and including octreotide (SMS 201-995) were found to bind with high affinity to SSTR2 receptors, which appear to be primarily of a pituitary type, and indeed affinities correlated extremely well with inhibitory potencies for inhibition of GH release from rat pituitary cells. Several new octapeptides were discovered with affinities and in vitro potencies greater than previously reported analogs. Whereas all of the octapeptides had much lower affinity for SSTR1 and SSTR3 receptors, which appear to be primarily present in the CNS, high affinity and highly specific ligands for the latter were found within a series of linear somatostatin analogs. No analogs were found which had high affinity for SSTR1 receptors. These studies confirm the feasibility of designing ligands which are specific for the various somatostatin receptors. These should provide useful tools for delineating the physiological roles of these receptors, specifically labeling certain receptors, and developing therapeutically interesting compounds targeted towards specific physiological events.