Linked Life Data

16625842

Source:http://linkedlifedata.com/resource/pubmed/id/16625842

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11 Suppl International
pubmed:dateCreated
2006-4-21
pubmed:abstractText
SOM230 is a novel somatostatin analog which shows affinity to 4 of the 5 known somatostatin receptors (SSTR1-5). In binding experiments, SOM230 has a higher affinity to SSTR1, SSTR3 and SSTR5 and a slightly lower affinity to SSTR2 compared to octreotide. In addition, SOM230 has a >7-fold longer plasma half-life than octreotide (11 vs 1.5 h). It was suggested that SOM230 with its broader binding and activity profile compared to octreotide should have a stronger (usually inhibitory) effect on the secretion of hormones. In several animal species, SOM230 was a more potent inhibitor of GH and IGF-I than octreotide. This is in line with a strong expression of both SSTR2 and SSTR5. In the pituitary of patients with primary Cushing's disease, the SSTR5 is more frequently expressed than SSTR2. Accordingly, in rats SOM230 caused a stronger inhibition of ACTH and corticosterone secretion than octreotide. In contrast, most recent experiments showed that octreotide was more potent than SOM230 to inhibit ghrelin secretion in rats. This effect could be explained by the strong expression of SSTR2 in the rat stomach, whereas expression of SSTR3, SSTR4 and SSTR5 was poor or absent. Based on these data it can be concluded that in tissues (or tumors), where several SSTRs are expressed, SOM230 will generally have a stronger effect than octreotide. In cases where SSTR2 is the most important receptor mediating a response (e.g. ghrelin release in rats), the stronger inhibitory effect of octreotide can be explained by its higher affinity for SSTR2. In contrast to the long-lasting inhibitory effect of SOM230 on GH and IGF-I secretion, the inhibitory effects of both compounds on ghrelin show strong tachyphylaxis. These data are in line with the hypothesis that activation of the SSTR2 alone results in a rapid desensitization of the response. If, however, additional SSTR subtypes (especially SSTR5) are expressed and activated by multiligand analogs like SOM230, this might not only form the basis for a stronger response, but also the basis for a reduced tachyphylaxis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adrenocorticotropic Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Corticosterone, http://linkedlifedata.com/resource/pubmed/chemical/Corticotropin-Releasing Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Ghrelin, http://linkedlifedata.com/resource/pubmed/chemical/Growth Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I, http://linkedlifedata.com/resource/pubmed/chemical/Octreotide, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hormones, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Somatotropin, http://linkedlifedata.com/resource/pubmed/chemical/Somatostatin, http://linkedlifedata.com/resource/pubmed/chemical/Thyrotropin, http://linkedlifedata.com/resource/pubmed/chemical/Thyrotropin-Releasing Hormone, http://linkedlifedata.com/resource/pubmed/chemical/pasireotide
pubmed:status
MEDLINE
pubmed:issn
0391-4097
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28-35
pubmed:dateRevised
2009-3-27
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Short- and long-term effects of octreotide and SOM230 on GH, IGF-I, ACTH, corticosterone and ghrelin in rats.
pubmed:affiliation
Novartis Institutes for BioMedical Research, Oncology Research, Basel, Switzerland. herbert.schmid@novartis.com
pubmed:publicationType
Journal Article, Comparative Study