L. Hofland, H. Visser-Wisselaar, S. Lamberts
Jul 31, 1995
Citations
1
Influential Citations
46
Citations
Journal
Biochemical pharmacology
Abstract
SRIFt was described originally by Krulich et al. [l] as a factor present in hypothalamic extracts capable of inhibiting GH release by cultured rat anteriorpituitarycells.Brazeauetal. [2]characterized this factor as a cyclic peptide (SS14) consisting of 14 amino acids. Several years later, a second bioactive form, an NHz-terminally extended somatostatin molecule, consisting of 28 amino acids (SS28), was isolated and characterized [3]. In mammals, both SS14 and SS28 originate from a 10.3 kDa prohormone called preprosomatostatin [4]. Somatostatin has an inhibitory action on a variety of physiological functions in different organ systems, including the hypothalamus, the anterior pituitary gland, the gastrointestinal tract, and the endocrine and exocrine pancreas [5]. In the brain, somatostatin may have a role in neurotransmission, both stimulatory and inhibitory [6,7]. On the basis of its widespread inhibitory actions, somatostatin may play a role in the treatment of human disease due to hyperfunction of the above organ systems. However, the clinical use of somatostatin was hampered because the native peptide had several disadvantages [S, 91. In particular, the need for continuous i.v. infusion due to its very short halflife in the circulation (< 3 min), its diversity of action (i.e. its potent inhibitory action on normal insulin secretion), and, finally, the rebound hypersecretion of hormones by normal tissues after 5514 infusion are major disadvantages [lo, 111. A logical step, therefore, was the development of structural analogs of somatostatin, not having the disadvantages of SS14 as described above. This research has led to