| Abstract: | Somatostatin (SRIF) is a hypothalamic tetradecapeptide which acts on several different types of pituitary cells to inhibit hormone release both in vivo and in vitro. We have previously shown that the GH4C1 clonal strain of rat pituitary tumor cells contains a single class of specific high-affinity SRIF receptors and that SRIF is a potent inhibitor of GH and PRL release by these cells. In this study, we have determined the relationship between the apparent binding affinity and biological potency of 19 SRIF analogs in GH4C1 cells. Receptor binding and biological activity were assayed under identical conditions. A good correlation (r = 0.96) was observed over a 10,000-fold range between the receptor binding affinities and biological potencies of SRIF analogs. Modifications at the C- and N-terminal regions of the SRIF molecule had minimal effects on binding to the receptor or potency to inhibit PRL release. However, substitution of residues 6 through 10 or reduction of the disulfide bond resulted in a 100-fold or greater decrease in both activities. The N-terminal extended SRIF analogs, SRIF-28, [D-Trp22]SRIF-28, and SRIF-25, were all somewhat less potent than SRIF. These results strongly support the involvement of the characterized SRIF receptor in initiating the biological actions of SRIF in GH4C1 cells and define the structural features of the SRIF molecule required for both receptor binding and activation. |
