ABSTRACT
I. INTRODUCTION Somatostatin is a neuropeptide that is widely distributed throughout the body. It was first identified as a growth hormone release-inhibiting factor synthesized in the hypothalamus. Outside the central nervous system (CNS), the peptide is present in endocrine as well as nonendocrine tissues. Somatostatin functions as a peptide with a generally inhibitory action in the central nervous and endocrine system. In the CNS it can act as a neurotransmitter, while in peripheral tissues it regulates endocrine and exocrine secretion and acts as a modulator of motor activity in the gastrointestinal tract (Reichlin, 1983, 1995; Brazeau, 1986). Somatostatin produced in the hypothalamus is transported through the portal circulation to the anterior pituitary, where it inhibits the secretion of growth hormone and other pituitary hormones such as thyroid-stimulating hormone. Somatostatin has also been shown to have antiproliferative effects in vitro (Schally, 1988). Somatostatin is secreted in two biologically active forms: a 14-amino-acid form (somatostatin-14) and an amino-terminally extended 28-amino-acid form (somatostatin-28). Native somatostatin has a plasma halflife of less than 3 minutes. Therefore, synthetic, metabolically stable analogues have been developed for clinical use. Structure-function analysis of native somatostatin and peptide analogues has shown that the amino acid residues Phe7, Trp8, Lys9, and Thr10 are necessary for receptor binding. A 14-amino-acid somatostatin-like neuropeptide, cortistatin, has been discovered in mouse brain tissue (de Lecea et al., 1996, 1997). The receptor-binding
site of cortistatin shares the same amino acid residues as somastostatin. Up to now, no specific cortistatin receptor has been identified, but differential effects in the CNS have been reported.
