Development of subtype selective ligands is essential for identifying the location of these receptors which is critical in gaining insights to their functions. Analysis of mRNA localization has its limitations because mRNA detection is not always a true reflection of receptor expression. This is most clearly shown in the case of sstr3, whose mRNA is highly expressed in the adult cerebellum, yet very little if any SRIF receptor binding is detectable in the cerebellum (20).
Recently, antibodies have been developed against some of the SRIF receptor subtypes, in particular sstr2, and have been useful in detecting expression of this receptor by immunoblotting (21,22). Development of antibodies and ligands for the other receptor should also facilitate their localizations.
Pharmacological studies have suggested that sstr2 is involved in mediating the inhibition of GH release by SRIF (14,15). The rank order of affinities of a large series of SRIF analogs to bind to cloned mouse sstr2 was similar to their rank order of potencies to inhibit GH release from rat pituitary cells in culture. In contrast, there was no clear correspondence between binding to the other receptors and inhibition of GH release. sstr2 mRNA and protein, as detected by immunoblotting are expressed in the anterior pituitary (1,20,21) consistent with the role of this receptor in controlling growth hormone secretion.
Several analogs with high affinity for sstr2, such as octreotide, are very effective in blocking GH release in human and rodents both from normal pituitaries as well as pituitary tumors. These analogs also bind to sstr5 (15), a receptor that is also likely to be expressed in anterior pituitary. However, the rank order of potencies of SRIF analogs to bind to rat sstr5 was not similar to their potencies to inhibit GH release. Furthermore, many SRIF analogs, such as octreotide, have relatively low affinity for human sstr5 (19), suggesting that their main mechanism of action in blocking GH secretion is via sstr2. Finally, sstr5 has been shown to exhibit higher affinity for SRIF 28 than SRIF. In contrast, SRIF 28 and SRIF are similar in potency in blocking GH secretion (14). These findings suggest that sstr2 is likely to be an important receptor in the control of GH secretion.
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