Receptor binding of somatostatin-28 is tissue specific

Abstract

Although somatostatin was originally identified in the hypo-thalamus as a tetradecapeptide (SRIF or S-14)¹, subsequent studies have revealed that tissue somatostatin is heterogeneous comprising in addition to S-14 two larger forms with molecular wieghts (M_rs) of 10,000–15,000 and 3,000 (refs 2–7). Recently a 28-amino acid peptide (somatostatin-28, S-28)—a 14-amino acid N-terminal extension of S-14—has been isolated from mammalian gut and hypothalamus^8–10. Synthetic S-28 (M_r 3,160) has been shown to correspond to the 3,000-M_r SLI species found in most tissues⁵ and to exhibit greater potency than S-14 for inhibiting both endocrine (growth hormone, insulin, glucagon)^11,12 and exocrine (pancreatic enzymes and bicarbonate) secretion¹³. It is not clear whether S-28 exerts similar effects to S-14 on central nervous system functions¹⁴ nor whether the S-14-like effects of S-28 are mediated through its conversion to S-14 or through direct action on the recently characterized S-14 receptors of rat brain and pituitary membranes^15,16. We suggest here that the greater potency of S-28 for inhibiting growth hormone secretion is because it binds to pituitary S-14 receptors with 3.2-fold higher affinity than does S-14. Furthermore in the central nervous system, S-28 has a lower affinity than S-14 for the receptors, indicating that it is less potent than S-14 in regulating brain functions. Receptor binding of S-28 in both pituitary and brain occurred directly without significant conversion to S-14, suggesting that S-28 is a true S-14 receptor agonist but possesses distinct tissue specificities.