Somatostatin receptor subtypes: targeting functional and therapeutic specificity.
Somatostatin is a regulatory peptide involved in a wide variety of biological functions throughout the body. A key physiological question, as well as the challenge to developing somatostatin-based therapeutics, is how functional specificity can be conferred in such a widespread, multifunctional hormonal system. With the discovery of distinct subtypes of the somatostatin receptor, we have attempted to elucidate the manner in which somatostatin selectively regulates specific biological functions using panels of somatostatin analogs that have been fully characterized for their unique selectivity and specificity for the various receptor subtypes. By testing these selective analogs in well-established biological assay systems, we and our collaborators have revealed functional interactions between the somatostatin receptor subtypes that can either potentiate or antagonize the cellular response to somatostatin. These observations have resulted in several novel concepts for treating acromegaly that should offer greater efficacy to a larger percentage of patients than current therapeutic options. Further, these studies are providing evidence of interaction between the somatostatin receptor subtypes and receptors of other G-protein-coupled receptor families. These various levels of interaction provide a means by which the cellular response to somatostatin can be exquisitely controlled and modified by both physiological status and disease. Greater understanding of these interactions will provide the conceptual basis for future therapeutics with enhanced efficacy and with greater cellular and functional specificity.
Culler
M D
MD
Biomeasure, incorporated/Beaufour - Ipsen Group, 27 Maple Street, Milford, MA 01757 USA.
Taylor
J E
JE
Moreau
J P
JP
D000818:Animals; D004298:Dopamine / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000037:antagonists & inhibitors; D006801:Humans; D017481:Receptors, Somatostatin / Q000187:drug effects*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000188:drug therapy
D006727:Hormone Antagonists; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; D013004:Somatostatin; D004298:Dopamine