Somatostatin actions

Panteris V, Karamanolis DG. The puzzle of somatostatin action, receptors, analogues and therapy. Hepatogastroenterology. 2005 52 1771-1781. 

REUBI, J.C., LAISSUE, J.A., Multiple pathways of somatostatin action in neoplastic disease. Trends Pharmacol. Sci. 16 (1995) 110-115. 

Biological Activities and Analogues. Somatostatin exerts some neurotropic actions, eg, as a tranquilizer and as a spontaneous motor activity depressor. It also lengthens barbiturate anesthesia time and induces sedation and hypothermia. These actions are consistent with the strong association between somatostatin and GABA in the primate cerebral cortex, 90—95% of somatostatin-positive ceHs also contain GABA (100). 

Capsaicin, an active ingredient in red pepper, is well known for its ability to release and deplete substance P in sensory C fibers. However, this action is not specific for substance P, as neurokinin A, calcitonin gene-related peptide (CGRP), and somatostatin also are released. 

Use of the first-generation somatostatin analog octreotide is limited by its extremely short duration of action and requirement for subcutaneous administration at least three times a day. If a patient s GH level returns to baseline before the end of an 8-hour dosing interval, the frequency of octreotide administration can be increased to every 4 to 6 hours. Most patients require octreotide in doses of 100 to 200 meg three times daily.19,20 To improve patient tolerance to gastrointestinal (GI) adverse effects, start octreotide at 50 meg every 8 hours.20 Assess IGF-I serum concentrations every 2 weeks after initiating therapy to further titrate dose in increments of 50 meg per dose. 

Cortistatin is synthesized as a precursor of 116 amino acids that gives rise to a C-terminal mature peptide, cortistatin-14 (CST-14), that shares 11 of its 14 residues with the neuropeptide somatostatin. However, the similarities between cortistatin and somatostatin are restricted to the mature peptides, which are the products of different genes. CST-14 binds to all five somatostatin receptors in vitro, although several authors suggest that CST-14 exerts its actions in vivo by binding to its own specific receptor (Spier de Lecea, 2000). 

Of the various peptides (e.g. the opioids, vasopressin, substance P and somatostatin) thought to be involved in the actions of carbamazepine, there is evidence that the reduction in the CSF concentration of somatostatin might be important in explaining its effects on cognition and also on the hypothalamo-pituitary-adrenal axis somatostatin is a major inhibitory modulator of this axis and h)rpercortisolism frequently occurs in patients following carbamazepine administration. 

Octreotide acetate (Sandostatin) is a synthetic peptide analogue of the hormone somatostatin. Its actions include inhibition of the pituitary secretion of growth hormone and an inhibition of pancreatic islet cell secretion of insulin and glucagon. Unlike somatostatin, which has a plasma half-life of a few minutes, octreotide has a plasma elimination half-Hfe of 1 to 2 hours. Excretion of the drug is primarily renal. 

Kakigi T, Tanimoto K, Maeda K The effect of various antidepressants on the concentration of somatostatin in the rat brain. Jpn J Psychiatry Neurol 44 145, 1990 Kalasapudi VD, Sheftel G, Divish MM, et al Lithium augments fos protoonocogene expression in PC 12 pheochromocytoma cells imphcations for therapeutic action of lithium. Brain Res 521 47-54, 1990... 

In view of the many actions of somatostatin that potentially have great therapeutic importance, a very large number of synthetic analogs have been prepared, with particular attention being given to overcoming the impracticably short half-life of the native hormone. 

Modifications designed to enhance the enzyme resistance and prolong the activity of SS derivatives have been quite successful. The use of D-amino acids instead of the normal L-enantiomers (e.g., in Trp ), or replacement of the disulfide link by a nonreducible ethylene bridge, leads to an increased duration of activity, approaching 3 hours. Several analogs show a greatly increased effect, like the [D-Ala, D-Trp ]somatostatin, which has 20 times the activity of SS on growth hormone release. The NH-terminal outside the cyclic dodecapeptide is not essential for activity. Selectivity of action results from... 

A. General description Octreotide is a long-acting cyclic octapeptide (molecular weight 1.0 kDa) with pharmacologic actions mimicking those of the natural hormone somatostatin. The usefulness of natural somatostatin is limited by its extremely short duration of action, which requires continuous infusion. Octreotide is a molecular form (an octapeptide with two D-amino-acid substitutions) that overcomes the problem of short duration of action. 

The clinical usefulness of somatostatin is limited by its short half-life in the circulation (3 minutes) when it is administered by intravenous injection. Octreotide is a synthetic octapeptide with actions similar to somatostatin. When administered intravenously, it has a serum half-life of 1.5 hours. It also may be administered by subcutaneous injection, resulting in a 6- to 12-hour duration of action. A longer-acting formulation is available for once-monthly depot intramuscular injection. 

Exerts pharmacological actions similar to the honnone somatostatin including ... 

Although GHRH has a predominant role in sleep regulation, other members of the somatotropic axis may also modulate sleep. Thus, several lines of evidence indicate that GH may stimulate REM sleep (35), and under chronic conditions, it may also stimulate NREM sleep, particularly the intensity of NREM sleep (36). The latter action might be mediated via IGF-1, which has a modest NREM-sleep-promoting activity (29). Finally, stimulation of somatostatin-2 receptors by somatostatin acutely inhibits NREM sleep (37). This action is attributed to an inhibition of GHRHergic neurons. In addition, somatostatin has been implicated in the promotion of REM sleep (38). 

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