Molecular Pharmacology of Somatostatin‐receptor Subtypes

Berthou, Christian; Weckbecker, Gisbert; Raulf, Friedrich; Kaupmann, Klemens; Schoeffter, Philippe; Hoyer, Daniel; Lübbert, Hermann

doi:10.1111/j.1749-6632.1994.tb17263.x

Cited by 153 publications

(101 citation statements)

References 38 publications

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“…Data were obtained from Patel and Srikant. 12 ‡The value is reported as 4.4 nM by Patel and Srikant, 12 31.6 nM by Bruns et al, 13 and 35 nM by Kubota et al 14 §Not all human tissues have been tested simultaneously. Data were obtained from Yamada et al, 8 Kaupmann et al, 15 Rohrer et al, 16 Panetta et al, 17 O'Carroll et al, 18 and Bell and Reisine.…”

Section: Acromegalymentioning

confidence: 99%

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Octreotide

et al. 1996

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Section: Acromegalymentioning

confidence: 99%

“…[12][13][14]23 Octreotide binds with a high affinity to somatostatinreceptor subtype 2 and subtype 5 and with a moderate affinity to subtype 3 but does not bind to subtypes 1 and 4. The binding characteristics of vapreotide and lanreotide are only slightly different, except with regard to subtype 4 (Table 1).…”

Section: S Omatostatin a Naloguesmentioning

confidence: 99%

Octreotide

et al. 1996

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“…Octreotide and lanreotide have a high affinity for the sst receptor subtype 2 (sst 2 ) and a modest affinity for sst 5 (Bruns et al 1994). However, expression of multiple sst subtypes is observed in NETs (Hofland & Lamberts 2003).…”

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Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study

Kvols¹,

Öberg²,

O'Dorisio³

et al. 2012

Endocrine-Related Cancer

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116

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Pasireotide (SOM230) is a novel multireceptor-targeted somatostatin (sst) analog with high binding affinity for sst receptor subtype 1, 2, 3 (sst 1,2,3 ) and sst 5 . Because of this binding profile, pasireotide may offer symptom control in patients with neuroendocrine tumors (NETs) and carcinoid syndrome no longer responsive to octreotide LAR. This was a phase II, open-label, multicenter study of pasireotide in patients with advanced NET whose symptoms of carcinoid syndrome (diarrhea/flushing) were inadequately controlled by octreotide LAR. Patients received s.c. pasireotide 150 mg twice daily (bid), escalated to a maximum dose of 1200 mg bid until a clinical response was achieved. Forty-four patients were evaluated for efficacy and 45 for tolerability. Pasireotide 600-900 mg s.c. bid effectively controlled the symptoms of diarrhea and flushing in 27% of patients. Evaluation of tumor response in 23 patients showed 13 with stable disease and ten with progressive disease at study end. The most common drug-related adverse events were nausea (27%), abdominal pain (20%), weight loss (20%), and hyperglycemia (16%) and most were of mild or moderate severity. Pasireotide 600-900 mg s.c. bid was effective and generally well tolerated in controlling the symptoms of carcinoid syndrome in 27% of patients with advanced NET refractory or resistant to octreotide LAR therapy.

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“…Pharmacological studies have shown that all 5 human subtypes bind somatostatin-14 and somatostatin-28 with high affinity, whereas the sst 2 subtype preferentially binds the octapeptide analog octreotide with very high affinity and is identical to the former SS1 subtype. Conversely, sst 1 and sst 4 do not bind octreotide-like substances, whereas sst 3 has an intermediate affinity (IC 50 5 30 nM) and sst 5 a rather high affinity (IC 50 5 7 nM) for octreotide (Bruns et al, 1994;Reisine and Bell, 1995). In a preliminary study (Reubi et al, 1994), we have evaluated the somatostatin receptor gene expression of sst 1 , sst 2 and sst 3 subtypes by in situ hybridization in 55 human primary tumors (meningiomas, neuroblastomas, pituitary adenomas, small cell lung carcinomas, lymphomas, breast tumors, carcinoids, islet cell carcinomas, medullary thyroid carcinomas and ovarian tumors), selectively chosen for their very high density of somatostatin receptors in binding assays.…”

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Somatostatin receptor subtypes sst1, sst2, sst3 and sst5expression in human pituitary, gastroentero-pancreatic and mammary tumors

et al. 1997

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Using in situ hybridization techniques with selective oligoprobes, the gene expression of sst 1 , sst 2 , sst 3 and sst 5 was studied in a series of 32 human pituitary adenomas, 28 breast tumors and 21 endocrine gastroentero-pancreatic tumors, shown to express somatostatin receptors to variable extents. In most of these tumors the sst 2 receptor subtype was abundantly expressed, even though a significant number of pituitary adenomas, breast and gastroentero-pancreatic tumors expressed sst 1 and/or sst 3 as well. A very high incidence of the sst 5 subtype was found in growth hormone-producing pituitary adenomas and, to a lesser extent, in inactive pituitary adenomas, whereas breast tumors seldom expressed sst 5 ; gastroentero-pancreatic tumors showed all possible combinations of sst expression, with, however, a predominance of sst 2 and sst 1 . Overall, the presence of sst 2 mRNA and/or sst 5 mRNA generally correlated with the presence of octreotide binding sites. A lack of octreotide binding sites corresponded with a lack of sst 2 mRNA. Several tumors exhibiting a low number of octreotide binding sites had no measurable sst 2 mRNA, despite abundance of b-actin mRNA, suggesting in these cases a very low abundance of sst mRNAs or a too low sensitivity of the in situ hybridization methodology. In all other cases, the method allowed precise localization of the respective mRNAs on the tumor tissue, notably in breast tumors with non-homogeneous receptor distribution. Tumors without measurable amounts of somatostatin receptors had no detectable sst mRNA. Our results indicate a highly variable abundance of the various sst mRNAs in individual somatostatin receptor-containing tumors.

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Molecular Pharmacology of Somatostatin‐receptor Subtypes

Cited by 153 publications

References 38 publications

Octreotide

Octreotide

Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study

Somatostatin receptor subtypes sst1, sst2, sst3 and sst5expression in human pituitary, gastroentero-pancreatic and mammary tumors

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