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説明
Originally isolated from hypothalamic tissue, somatostatin is characterized as an inhibitor of growth hormone (GH) release.
The structure was determined in 1971. Subsequent investigations led to the recognition that somatostatin also was
released from the pancreas and has a role of inhibiting the secretion of both insulin and glucagon. A total of five
somatostatin receptor subtypes have been characterized and cloned (sst1 to sst5).
Subtype sst4 is associated with the
inhibition of insulin release, and an sst4-selective inhibitor has been reported. The somatostatin analogue SOM230
has exhibited selectivity for sst1, sst2, sst3, and sst5 in rats and effectively decreased plasma GH and insulin-like growth
factor-1 (IGF-1) levels by 75% without significant effects on insulin or glucagon. Another analogue, PT R3173, with
selectivity for recombinant human somatostatin receptor (hsst2, hsst4, hsst5) was substantially more effective in inhibiting
GH secretion compared to glucagon and insulin release in rats.
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使用
Somatostatin is a peptide hormone that regulates the endocrine system. Extensive SS analogs with improved pharmacokinetics, bioavailability, and receptor subtype selectivity have been developed. These include nonpeptidergic analogs and octapeptides such as octreotide and lanreotide. Octreotide and lanreotide are long-acting sst2-preferring agonists, and are used for the treatment of acromegaly, gastroenteropancreatic tumors, neuroendocrine tumors, and other gastrointestinal disorders such as secretory diarrhea and gastrointestinal bleeding.
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適応症
Somatostatin (or somatotropin release–inhibiting factor
[SRIF]) occurs primarily as a 14–amino acid peptide,
although a 28–amino acid form also exists.As with
the other hypothalamic peptides, it is formed by proteolytic
cleavage of a larger precursor. Somatostatin, originally
isolated from the hypothalamus, is also in many
other locations, including the cerebral cortex, brainstem,
spinal cord, gut, urinary system, and skin.
Somatostatin inhibits the secretion of many substances
in addition to growth hormone.
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一般的な説明
Somatostatin was discovered in the hypothalamus. It is elaboratedby the δ-cells of the pancreas and elsewhere in thebody. Somatostatin is an oligopeptide (14 amino acidresidues) and is referred to as somatotropin release–inhibitingfactor (SRIF).
Its primary action is inhibiting the release of GH from thepituitary gland. Somatostatin also suppresses the release ofboth insulin and glucagon. It causes a decrease in bothcAMP levels and adenylate cyclase activity. It also inhibitscalcium ion influx into the pituitary cells and suppressesglucose-induced pancreatic insulin secretion by activatingand deactivating potassium ion and calcium ion permeability,respectively. The chemistry, SARs, and potential clinicalapplications have been reviewed.
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臨床応用
Somatostatin has a very brief half-life in serum and
is not useful clinically.An 8–amino acid analogue with 2
D-amino acids substituted for the naturally occurring
L-amino acids is more stable, and monthly injections of
a depot form of this analogue (octreotide, Sandostatin
LAR) have several uses. Long-acting octreotide is used
to treat acromegaly, as described earlier. It is also used
to counteract unpleasant effects caused by overproduction
of secreted bioactive substances produced by neuroendocrine
tumors, including hyperinsulinemia from
insulinomas and secretions from carcinoid tumors that
cause severe diarrhea. Octreotide may also control severe
diarrhea associated with AIDS that has not responded
to other treatments.
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副作用
Somatostatin analogues (SSA) are a common treatment for some forms of neuroendocrine tumours (NETs). Somatostatin analogues are usually well tolerated which means you may not have many side effects.
The main side effects are
Loss of appetite
Feeling sick
Feeling bloated
Stomach pain
Fatigue (tiredness)
Increased diarrhoea (this is rare)
Soreness at the injection site
Uncommon side effects include sinus bradycardia, asthenia, headache,pruritus, decreased libido, increased serum bilirubin, and constipation.
Transient side effects, gastrointestinal discomfort and decreased glucose tolerance, usually last only a few weeks after initiation of therapy.
The most significant side effect associated with prolonged use of octreotide is formation of gallstones resulting from reduced bile flow.
