Chapter category: Adhesion Molecules
Somatostatin Analogs: Lessons in Functional Complexity and Receptor Interactions
Somatostatin Analogs in Diagnostics and Therapy
Edited by: Marek PawlikowskiISBN: 978-1-58706-223-0
» Get more information about this book at landesbioscience.com «
Chapter authors:
Michael D. Culler
Somatostatin (SST) was originally isolated from the hypothalamus as the key suppressor GH secretion, but is now known to be widely distributed throughout the body and to be involved in numerous physiological functions. While the varied activity of SST creates opportunities for its use as a therapeutic agent, it also hampers drug development by creating the potential for inducing undesired actions. The discovery of five distinct somatostatin receptor (SSTR) subtypes has provided an opportunity for creating subtype-specific, and, potentially, action-specific SST analogs. Through efforts to determine the functional association between receptor subtype and function, it has become apparent that most SST-responsive target tissues express multiple receptor subtypes, and that it is the interaction of the subtypes that will determine the cellular response. In this regard, we have observed both action-enhancing and antagonistic interactions between different SSTR subtype combinations, and that these effects can be induced in a gradated fashion depending on the degree to which the different subtypes present are activated. These observations imply that the cellular response to SST is dictated by the ratio of receptor subtypes present on the cell at a given moment. In this way, the cellular response to SST can be influenced by the prevailing environmental conditions, physiological status and hormonal milieu, through alteration of the ratio of receptor subtypes expressed. One can also envision the development of pathologies in which the cellular response is inappropriate due to altered ratios of receptor subtype expression. The concept of receptor interaction attains even greater complexity with the demonstration that the SSTR subtypes can also interact with members of other receptor families. These complex interactions provide potential opportunities for creating drugs that target only specific combinations of receptors that are expressed under the appropriate conditions to generate a specific cellular response. Learning to unravel this complex cellular code is key, both for furthering our understanding of cellular based physiology and disease, and in order to create more effective drugs with greater functional specificity.
Additional chapters from this book:
Somatostatin Analogs—New Perspectives
Gabriela Melen-Mucha and Marek Pawlikowski
Acromegaly and so-called neuroendocrine tumors (carcinoids, pancreatic endocrine tumors) are at present the only routine indications for somatostatin (SST) analogs therapy. However, the progre...
The Treatment of Acromegaly with Somatostatin Analogs
Nuria Sucunza, Mª José Barahona and Susan M. Webb
Although transsphenoidal surgery of pituitary micro or macroadenomas is the treatment of choice in most acromegalic patients, somatostatin analogs are the first choice for medical treatment, eit...
Somatostatin Receptors: Distribution in Normal Tissues and Transduction Mechanisms
Gabriela Melen-Mucha and Slawomir Mucha
receptors belonging to the family of G protein coupled receptors. So far five SST receptor subtypes (sst1-5) have been cloned and characterized. The genes for these receptor subtypes are localized...
Somatostatin Receptors in Human Tumors: In Vitro Studies
Marek Pawlikowski
Neoplastic cells express and often even over-express the somatostatin receptors. It is important because the presence of sst receptors predicts—to some extent—the possibility of treatment with...
Physiology of Somatostatin
Marek Pawlikowski
Somatostatin (SST) was originally discovered as a hypothalamic peptide which inhibits growth hormone (GH) secretion from the pituitary gland. It appears in two molecular forms, composed from 14 ...
The Treatment of Neuroendocrine Tumors (NET) with Somatostatin Analogs
Beata Kos-Kudla
There is increasing interest in somatostatin (SST) analogs in the diagnosis and therapy of neuroendocrine tumors (NET), which constitute a heterogeneous group of neoplasms often associated with ...
Somatostatin Analogs: Lessons in Functional Complexity and Receptor Interactions
Michael D. Culler
Somatostatin (SST) was originally isolated from the hypothalamus as the key suppressor GH secretion, but is now known to be widely distributed throughout the body and to be involved in numerous ...
Radiolabeled Somatostatin Analogs in the Diagnosis and Therapy of Neuroendocrine Tumors
Leszek Królicki, Jolanta Kunikowska and Marianna I. Bak
The proof of the principle, that many tumors are characterized by a high expression of somatostatin receptors, has provided the background for the use of somatostatin analogs in the diagnostic process...
