Comparison of the gastric exocrine inhibitory activities and plasma kinetics of somatostatin-28 and somatostatin-14 in cats

Hirst, Barry H.; Conlon, J. Michael; Coy, David H.; Holland, Joy; Shaw, B.

doi:10.1016/0167-0115(82)90115-x

Cited by 33 publications

(15 citation statements)

References 30 publications

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“…(Meyers et al, 1980;Brazeau et al, 1981;Hirst et al, 1982) but the potential importance of metabolism was largely ignored (Gu et al, 1992). The relative binding affinities of metabolically more stable analogues such as octreotide and seglitide (MK 678) (Tran et al, 1985;Raynor & Reisine, 1989; has been used as the basis for the subclassification of somatostatin receptors into SRIF, and SRIF2.…”

Section: Influence Of Antagonistsmentioning

confidence: 99%

Characterization of somatostatin receptors in guinea‐pig isolated ileum, vas deferens and right atrium

Feniuk

Dimech

Humphrey

1993

British J Pharmacology

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1 Somatostatin14 (SS14) inhibits neurogenically mediated contractile responses in guinea-pig ileum and vas deferens and exerts a direct negative inotropic action in guinea-pig spontaneously beating right atrium. In this study, the receptors mediating these inhibitory effects have been characterized by comparing the potencies of several cyclic somatostatin analogues. 2 In the guinea-pig ileum, SS14, somatostatin28 (SS28), somatostatin25 (SS25) and several smaller cyclic somatostatin analogues including octreotide, angiopeptin and CGP 23996, inhibited neurogenically mediated contractile responses, each being of similar potency. 3 In contrast, in the guinea-pig vas deferens and right atrium, SS28 was about 30 times more potent than SS14. However, although angiopeptin was nearly as potent as SS14 as an agonist in the vas deferens, in guinea-pig atrium angiopeptin had low intrinsic activity and antagonized the negative inotropic action of both SS14 and SS28 (pKB values of 7.4 and 7.2, respectively). CGP 23996 was 2-7 times weaker than SS14 in guinea-pig vas deferens and atria.4 Phosphoramidon (1 AM) and amastatin (10 JAM) did not influence the potency of SS14 or SS28 in either the guinea-pig ileum or right atrium. In the guinea-pig vas deferens, phosphoramidon and amastatin did not affect the potency of SS28, but enhanced the potency of SS14 about 5 fold. Despite the presence of phosphoramidon and amastatin, SS28 was still more potent than SS14 in the vas deferens. 5 The putative somatostatin receptor blocking drug, cyclo(7-aminoheptanoyl Phe-D-Trp-Lys-Thr[Bzl]) (CPP; 1 JAM), did not antagonize the effects of either SS14 or SS28 in ileum, vas deferens or atrial preparations. 6 Somatostatin14 did not modify the contractile action of carbachol or ax,-methylene ATP in the ileum and vas deferens respectively, suggesting that the site of the inhibitory effects on neurogenically mediated contractile responses in both preparations was pre-junctional. Consistent with this conclusion was the observation that the inhibitory effect of SS14 was markedly and inversely related to the external Ca2+ concentration. The inhibitory effect of SS14 in guinea-pig atrium was only partly dependent on the external Ca2+ concentration. 7 The somatostatin receptors mediating the inhibitory effect of SS14 in the ileum and vas deferens can be distinguished by the differential relative potencies of SS14 and SS28. In the former, SS14 and SS28 have similar potency whilst in the latter SS28 is much more potent. In this respect, the somatostatin receptor mediating negative inotropy in the guinea-pig right atrium appears similar to that identified in the vas deferens.8 We suggest that the somatostatin receptor mediating inhibition of neurogenic contraction in the ileum is similar to the recently cloned SSTR2 receptor. In contrast, the somatostatin receptor mediating negative inotropy in the atrium and inhibition of neurotransmission in the vas deferens appears similar to the SSTR4 receptor which recognises SS28 with higher affinity than SS14.

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Section: Influence Of Antagonistsmentioning

confidence: 99%

Characterization of somatostatin receptors in guinea‐pig isolated ileum, vas deferens and right atrium

Feniuk

Dimech

Humphrey

1993

British J Pharmacology

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“…Somatostatin-14 is more potent than somatostatin-28 as an inhibitor of gastric exocrine secretions [8], When expressed in terms of exogenous doses, somatostatin-14 is three to four times more potent than somatostatin-28. The difference is, however, enhanced to eight to nine times when expressed in terms of circulating concentra tions of the two forms of somatostatin; e.g.…”

Section: Gastric Inhibitory Activities Of Somatostatin-14 and Somatosmentioning

confidence: 99%

“…Increasing doses of somatostatin or ana logue are then added to the infusion, and the difference between secretory rates on control, without somatosta tin, and test, with somatostatin, experiments the dose of somatostatin required for 50% inhibition (ID50) can be determined. Over a number of years, we have found somatostatin to be a potent inhibitor of gastric acid secretion, as assayed by this method, with an ID50 of around 1.2-1.7 nmol/kg/h [6][7][8], With pentagastrin as the stimulant of gastric secretions, somatostatin is ap proximately five times more potent an inhibitor of pep sin secretion compared with its effect on acid secretion [3,[5][6][7][8]. This apparent greater potency of somatostatin against pepsin secretion is due to the poor pepsin-stimu lating activity of pentagastrin, rather than any specific effect of somatostatin; somatostatin is equipotent against acid and pepsin secretions stimulated by insulin, a much more potent stimulant of pepsin secretion [9],…”

Section: Assay Of Gastric Inhibitory Potency Of Somatostatin and Analmentioning

confidence: 99%

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Somatostatin Structure-Activity Studies in the Stomach

et al. 1988

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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.

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“…Six healthy fasting volunteers (all males, age [23][24][25][26][27][28][29][30] Exocrine pancreatic secretion studies. After fasting overnight, the subjects swallowed a multilumen tube using standard methods previously described (7).…”

Section: Methodsmentioning

confidence: 99%

Circulating somatostatin. Physiological regulator of pancreatic function?

K¹,

Beglinger²,

Köhler³

et al. 1987

J. Clin. Invest.

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The present study was designed to determine whether somatostatin is released into the circulation in sufficient amounts to regulate exocrine and endocrine pancreatic function and to evaluate the possible role of somatostatin as a hormonal regulator of the pancreas. Mean plasma somatostatin levels (SLI) increased from 11±2 pmol liter-' to peak concentrations of 18±2 in six healthy male volunteers after a steak meal (P < 0.05). Infusion of somatostatin inhibited hormone-induced exocrine pancreatic secretion and suppressed cerulein-stimulated pancreatic polypeptide (PP) secretion, but did not significantly change arginine-stimulated insulin and glucagon release at mean plasma somatostatin concentrations within the range seen after a meal. The amount of somatostatin released after a meal thus was of sufficient magnitude to inhibit exocrine pancreatic function and PP release. On the other hand, basal and arginine-stimulated glucagon and insulin secretions were not significantly affected by these plasma concentrations of intravenous somatostatin suggesting that the exocrine pancreas might be more sensitive to somatostatin than the islet cells. We conclude that somatostatin in concentrations within the range seen after a meal is a potent inhibitor of stimulated acinar cell function in man. The findings support the hypothesis that somatostatin acts as a true hormonal regulator.

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Comparison of the gastric exocrine inhibitory activities and plasma kinetics of somatostatin-28 and somatostatin-14 in cats

Cited by 33 publications

References 30 publications

Characterization of somatostatin receptors in guinea‐pig isolated ileum, vas deferens and right atrium

Characterization of somatostatin receptors in guinea‐pig isolated ileum, vas deferens and right atrium

Somatostatin Structure-Activity Studies in the Stomach

Circulating somatostatin. Physiological regulator of pancreatic function?

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