Inactivation of somatostatin (GH‐RIH) and its analogs by crude and partially purified rat brain extracts

Marks, Neville; Stern, F.

doi:10.1016/0014-5793(75)80996-3

Cited by 69 publications

(20 citation statements)

References 10 publications

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“…We have not examined hepatic degradaion of somatostatin, but it is highly likely that rather than accumulate unchanged in the liver, the peptide is ultimately cleaved into small fragments. This has been demonstrated with homogenates of brain (40), and in blood (1,4,16). Further studies on this point are needed.…”

Section: Calculatiotismentioning

confidence: 87%

Clearance of Immunoreactive Somatostatin by Perfused Rat Liver

Sacks¹,

Terry²

1981

J. Clin. Invest.

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Section: Calculatiotismentioning

confidence: 87%

Clearance of Immunoreactive Somatostatin by Perfused Rat Liver

Sacks¹,

Terry²

1981

J. Clin. Invest.

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“…Although it is known that somatostatin has a very short half-life o f 2 -4 min Vale et al, 1975), the only reports o f its enzymic inactivation are by Marks and Stern (1975) and by Griffiths et al (1976d, e). Marks and Stern (1975) showed that somatostatin was inactivated by crude and partially purified peptidases in a supernatant fraction from whole rat brain.…”

Section: Growth Hormone Release-inhibiting Hormonementioning

confidence: 99%

Peptidase Inactivation of Hypothalamic Releasing Hormones

Griffiths¹

1976

Horm Res

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With the structural characterization of the hypothalamic hormones, luteinizing hormone-releasing hormone (LH-RH), thyrotrophin-releasing hormone (TRH), melanocyt-stimulating hormone release-inhibiting hormone (MIH), and growth hormone release-inhibiting hormone, (GH-RIH or somatostatin), it has been possible to investigate their enzymic inactivation by peptidases which are present at various sites in the body. Enzymes may play an important part in the control of polypeptide hormone levels and the peptidases acting on these four hypothalamic hormones may regulate the amount of TRH, LH-RH, MIH and somatostatin released from the hypothalamus, or their action at the level of the pituitary and their removal from the circulation. By studying the peptidase enzymes, further information may be obtained on the physiological mechanisms controlling the secretion and actions of hypothalamic hormones, as well as on the design of analogues with increased or competitive activity.

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“…In the case of somatostatin, at least 5 sites of enzymatic degradation are known ( fig. 1) [27]. The most dangerous cleavage can occur after Trp 8 because such a rupture leads to completely inactive fragments.…”

Section: Somatostatin Analogs: Chemistry and Pharmacokineticsmentioning

confidence: 99%

Somatostatin Analogs for Cancer Treatment and Diagnosis: An Overview

Scarpignato

Pelosini

2001

Chemotherapy

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Due to the limited efficacy and considerable toxicity of conventional chemotherapy, novel cytotoxic agents and innovative noncytotoxic approaches to cancer treatment are being developed. Amongst the various hormonal agents, increasing attention is being directed to somatostatin analogs. This is largely due to the demonstration of antineoplastic activity of these compounds in a variety of experimental models in vitro and in vivo and to the elucidation of some aspects of the molecular mechanisms underlying their antineoplastic activity. On the other hand, clinical experience with somatostatin analogs in the treatment of conditions like acromegaly and GEP tumors has shown that they are well tolerated compared to other antineoplastic therapies currently in use. As a consequence, there is much ongoing clinical research to determine whether or not results from experimental studies will translate into clinically useful antineoplastic activity. Besides being used in cancer treatment and palliation, radiolabelled somatostatin analogs are employed for the localization of primary and metastatic tumors expressing somatostatin receptors. The so-called ‘somatostatin receptor scintigraphy’ is indeed the most important clinical diagnostic investigation for patients with suspected neuroendocrine tumors. Targeted radiotherapy, which is being evaluated in clinical trials, represents an obvious extension of somatostatin scintigraphy. Since the short half-life of native somatostatin makes continuous intravenous infusion mandatory, several long-acting analogs have been synthesized. Amongst the hundreds of peptides synthesized, octreotide (which binds mainly to SSTR-2 and SSTR-5 receptor subtypes) has been the most extensively investigated. A thorough analysis of the pharmacological activities and therapeutic efficacy of the native somatostatin and the synthetic analogs (octreotide, lanreotide and vapreotide) reveals that the biological actions of these peptides are not always identical. These differences appear to be related to the different affinities of the natural hormone and synthetic derivatives for the different receptor subtypes. For all the three peptides long-lasting formulations have been developed to provide patients with the convenience of once or twice a month administration and to ensure stable drug serum concentrations between injections. Radiolabelled derivatives of octreotide, lanreotide and vapreotide have been synthesized and used as radiopharmaceuticals for somatostatin receptor scintigraphy and somatostatin receptor-targeted radiotherapy. The safety profile of synthetic somatostatin analogs is well established. Most adverse reactions to these peptides are merely a consequence of their pharmacological activity and consist mainly of gastrointestinal complaints, cholelithiasis and effects on glucose metabolism. They are often of little clinical relevance, thus making somatostatin analogs safe drugs for long-term use. While immediate release preparations are the drugs of choice in the short term, long-acting formulati...

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Inactivation of somatostatin (GH‐RIH) and its analogs by crude and partially purified rat brain extracts

Cited by 69 publications

References 10 publications

Clearance of Immunoreactive Somatostatin by Perfused Rat Liver

Clearance of Immunoreactive Somatostatin by Perfused Rat Liver

Peptidase Inactivation of Hypothalamic Releasing Hormones

Somatostatin Analogs for Cancer Treatment and Diagnosis: An Overview

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