ISSN:1663-2818    

DOI:10.1159/000180964

出版商:S. Karger AG    

年代:1988

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000180965

出版商:S. Karger AG    

年代:1988

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000180966

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Following the discovery and biochemical characterization of natural somatostatin its action profile has been thoroughly investigated. Although the name somatostatin was coined in virtue of its growth hormone release-inhibiting properties, a number of central and peripheral endocrine and paracrine actions have been ascribed to this peptide. Its inhibitory effect on a series of pituitary and gastrointestinal hormones has characterized somatostatin as a classical brain-gut hormone. Circulating and tissue levels of somatostatin and its possible physiological role are analyzed and clinical implications are drawn.

ISSN:1663-2818    

DOI:10.1159/000180967

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Objective of peptide chemistry has always been the production of analogues for clinical application. Advantages sought over natural peptides are (a) reduced molecular size; (b) prolonged biological half-life, and (c) enhanced specificity. After elucidation of the active core of somatostatin a number of analogues have been synthetized. Among them SMS 201-995, an octapeptide, was selected for further development because of its high potency and prolonged plasma clearance. Procedures extending the duration of action of somatostatin derivatives such as enhancement of lipophilicity and amino acid substitution are described, and factors influencing the specificity of such substances are succinctly analyzed.

ISSN:1663-2818    

DOI:10.1159/000180968

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The chain of events leading to the manifestation of the biological action of somatostatin are described. Internalization is mediated by cytoskeletal proteins in the presence of calmodulin. Transduction of the somatostatin message at the membrane level takes place through inhibition of cyclic AMP accumulation and blockade of cytosol calcium increases. The influence of central and peripheral factors upon these processes is discussed and the importance of the Ni/Ns components is stressed. Thus, somatostatin also suppresses phosphoinositide turnover and stimulates soluble phosphodiesterase, thus reinforcing its negative effect on cyclase generation.

ISSN:1663-2818    

DOI:10.1159/000180969

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Somatostatin receptors have been visualized with autoradiography and characterised biochemically in various somatostatin target tissues, such as brain, pituitary, pancreas and gastrointestinal tract, where they are likely to mediate the somatostatin actions. With the same methods, somatostatin receptors have been detected also in tumors originating from somatostatin target tissues: high receptor incidence is found in GH-producing pituitary adenomas as well as in some hormone-producing gastrointestinal tumors. These tumors are often highly responsive to somatostatin analogs in vivo. Among brain tumors, meningiomas usually contain a high density of receptors, suggesting a novel function for somatostatin in the human meninges. Among other human tumors tested, prostate, ovarian and endometrial carcinomas were free of receptors whereas 3 out of 39 mammary tumors contained somatostatin receptors.

ISSN:1663-2818    

DOI:10.1159/000180970

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Somatostatin plays an important role in the regulation of the episodic and ultradian rhythm of growth hormone (GH) secretion. Passive immunization of rats with specific antibodies to the 14 and 28 amino acid sequences caused a significant GH elevation. The fact that somatostatin antiserum was unable to block episodic GH surges indicates that this hormone’s release must be regulated by a dual mechanism. Indeed, GH-releasing factor (GRF) seems to be instrumental in the maintenance of pulsatile GH secretion. Moreover, exogenous GRF induced a further GH increase predominantly during the period of active secretion. Neutralization of endogenous somatostatin eliminated this time-dependent effect, indicating that this peptide blocks periodical spontaneous GH release. Food deprivation and changes in glucose homeostasis virtually obliterate the ultradian GH rhythm. In this context, peripheral somatostatin seems to play an important role. Also the central GRF/somatostatin interplay is responsible for a short-loop feedback control on pituitary somatotrop

ISSN:1663-2818    

DOI:10.1159/000180971

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Somatostatin participates in the regulation of nutrient entry from the intestinal tract into the circulation. Thus, dietary fats and proteins may elicit significant increases of gastropancreatic somatostatin. Regulation of postprandial somatostatin secretion may occur via neural, hormonal and humoral factors. This peptide, in pharmacological doses, inhibits virtually all gastrointestinal exo- and endocrine functions as well as local motor activity. Neutralization of endogenous circulating somatostatin with specific antiserum is followed by increases in GH and enteroglucagon, augmenting also the postprandial rise of gastrin, insulin and pancreatic polypeptide. Somatostatin deficiency can be observed in obese subjects with hyperinsulinism. Concomitant elevation of insulin and gastrin levels can be antagonized by exogenous somatostatin. These findings confirm the importance of somatostatin as a peripheral regulator in experimental and human biology.

ISSN:1663-2818    

DOI:10.1159/000180972

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Somatostatin may inhibit gastric exocrine functions independent of blockade of gastrin secretion. In order to further investigate this suppressive effect, somatostatin derivatives were injected to cats bearing a cannulated gastric fistula under pentagastrin stimulation. Results showed that somatostatin-14 was more potent than somatostatin-28 in this particular model. Analogues with substituted residues exhibited a variable spectrum of actions on hormone release and gastric function. A cyclic pentapeptide was deprived of gastric or GH inhibitory properties whereas the related peptide with a benzyl-protecting group on Thr was only devoid of gastric effect. The octapeptide SMS 201-995 was described as a potent inhibitor of gastric secretion in comparison with natural somatostatin in rats and also in humans, but was unable to induce maximal suppression of acid output in the cat model. Differences in gastric effect of different derivatives could be explained on the basis of binding to a selective subset of receptors, since at least two binding sites have been identified in the stomach mucosa. Serial studies with short cyclic somatostatin should help to establish a clear relationship between peptide structure and inhibition of gastric secretion.

ISSN:1663-2818    

DOI:10.1159/000180973

出版商:S. Karger AG    

年代:1988

数据来源: Karger