Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Salivary, gastric, and pancreatic secretory responses to intravenous 13-norleucine-motilin (13-nle-motilin), a synthetic analog of motilin and biologically equivalent to the natural polypeptide, were studied in healthy volunteers. 13-nle-Motilin in doses of 100 ng/kg body wt/hr significantly stimulated gastric pepsin output, while H + secretion and serum gastrin levels remained unchanged. Enhanced pepsin secretion was not accompanied by an increase in gastric secretion of cyclic 3', 5'-adenosine monophosphate, nor did gastric mucosal levels of the cyclic nucleotide rise. A dose of 13-nle-motilin, which stimulated gastric pepsin output, did not exert any significant effect on salivary and pancreatic secretions.
 ...
PMID:Effects of 13-nle-motilin on salivary, gastric, and pancreatic secretions in man. 18 98

1. In dogs with gastric fistulas and vagally innervated fundic and antral pouches, 13-norleucine-motilin (13-nle-motilin), a synthetic analogue of motilin, infused intravenously in graded doses produced a dose-dependent increase in gastric acid and pepsin outputs. 2. The motilin-induced stimulation of gastric secretion occurred independently of antral pH and was not accompanied by any alteration in the serum gastrin level suggesting that motilin did not affect the release of gastrin. 3. When infused intravenously in a constant dose against a constant background stimulation with pentagastrin or histamine 13-nle-motilin inhibited both acid and pepsin secretion from the main stomach and fundic pouch. 4. The inhibitory effect of 13-nle-motilin was always associated with a marked reduction in mucosal blood flow but without any change in the ratio of aminopyrine concentration in the gastric juice and blood plasma indicating that this peptide primarily affected gastric secretion but did not limit the gastric mucosal microcirculation.
 ...
PMID:Effect of 13-NLE-motilin on gastric secretion, serum gastrin level and mucosal blood flow in dogs. 32 55

Motilin is a polypeptide containing 22 amino-acids from the entero-chromaffin cells of the mucosa of the small intestine. Synthetic analogues (13-norleucine-motilin; 13-leucine-motilin) proved to be equal to the natural polypeptide in the biological aspects. Motilin primarily stimulates the motility of the upper gastrointestinal tract but inhibits gastrin evacuation. The contractile action of motilin does not take place by way of the nerves but through receptors on or in the smooth muscle cell itself. Motilin and cyclic adenosine-3':5'-monophosphate are functional antagonists in the contraction of the gastrointestinal musculature. Depending on the dosis, motilin increases gastric pepsin secretion and inhibits protein biosynthesis in the gastric mucosa itself. Radioimmunological motilin tests will help to determine which of the above-mentioned motilin actions are "physiological" and which of them merely "pharmacological".
 ...
PMID:[Motilin-range and analysis of its action]. 78 38

Gastrointestinal myoelectric activity was studied in three conscious fasted dogs with electrodes surgically implanted in the stomach and small intestine, during separate and combined intravenous infusions of 13-norleucine motilin (13-nle-motilin) and pentagastrin (PG). Basal recordings confirmed the presence of regular interdigestive myoelectric complexes (MC's). 13-nle-motilin infusion below 50 ng/kg-h was without effect: higher doses up to 400 ng/kg-h resulted in the interpolation of one or more MC's in the spontaneous sequence. The rate of aboral transit of 13-nle-molitin-induced MC's did not differ significantly from that of spontaneous MC's. When MC's were abolished by feeding or PG infusion, simultaneous 13-nle-motilin administration was without effect on spike activity, but slightly attenuated the accelerating effect of gastrin on the gastric pacemaker frequency. The myoelectric events triggered by 13-nle-motilin suggest that in the conscious dog the polypeptide may not act directly on the smooth muscle cell, as it does in vitro, but through an extra-enteric neural control mechanism which is uncoupled by gastrin.
 ...
PMID:The gastrointestinal myoelectric response to 13-Nle-motilin infusion during interdigestive and digestive states in the conscious dog. 90 76

Under endoscopic control, biopsy specimens were taken from the oxyntic gland area of the stomach before and after administration of pentagastrin, synthetic secretin, and 13-norleucine motilin (13-nle-motilin), respectively. In 29 volunteers, the basal rate of 14C-leucine incorporation into mucosal protein averaged 41.2 +/- 7.7 X 103 cpm/mg protein (mean +/- S.D.). One and 4 hours after s.c. administration of pentagastrin (6 mug/kg body weight), values were significantly increased (p less than 0.05) by 18.9 and 21.8%, respectively, with respect to the basal level. One hour after an intravenous shot of 2 CU per kg body weight of secretin, gastric mucosal protein synthetis was not substantially inhibited, whereas a 1-hour continuous i.v. infusion of 13-nle-motilin (0.4 mug/kg body weight, hr) significantly decreased 14C-leucine incorporation rates by 17.5% (p less than 0.05). In contrast to rats, 1 hour after s.c. pentagastrin, protein synthesis in human duodenal mucosa was not altered. From these results it may be concluded that pentagastrin has a trophic influence on gastric mucosa in man. Moreover, the data presented are compatible with the hypothesis that gastrin and motilin may be involved in the regulation of human gastric mucosal protein synthesis.
 ...
PMID:Effects of in vivo administration of pentagastrin, secretin, and 13-Nle-Motilin on the in vitro incorporation of 14C-leucine into protein of human gastric mucosa. 99 30

This study in man (n = 35) deals with the effects of in vivo administration of pentagastrin, synthetic secretin, and 13-norleucine-motilin (13-nle-motillin), respectively, on the in vitro incorporation of 14C-leucine into gastric mucosal protein. From the results presented it may be concluded that pentagastrin has a trophic influence on gastric mucosa in man, too, while protein synthesis in human duodenal mucosa remains unaltered. As the incorporatin of 14C-leucine into gastric mucosal protein is inhibited both by secretion and 13-nle-motiln, it may be hypothesised that secretin and motilin act as functional antagonists of gastrin in the regulation of human gastric mucosal protein synthesis.
 ...
PMID:Protein synthesis in human gastric mucosa: effects of pentagastrin, secretin, and 13-nle-motilin. 119 72

The leucosulfakinins (LSKs), isolated from head extracts of the cockroach Leucophaea maderae, are sulfated neuropeptides with homology to gastrin and cholecystokinin. The undecapeptide LSK and decapeptide LSK-II stimulate contractions of the isolated cockroach hindgut. Several structural aspects of the two gastrin/CCK-like insect leucosulfakinins (LSKs) and their relation to FMRF-amide are discussed. Replacement of the oxidation sensitive Met residue with isosteric norleucine leads to an analog with retention of biological activity. The Arg residue of the LSKs is critical for cockroach hindgut contractile stimulatory activity, as its introduction into gastrin II transforms the inactive peptide into an active analog. As demonstrated by the equipotent [His14,Arg16]gastrin II, the His8 and Asp5 residues of LSK are not critical for activity. The common C-terminal tetrapeptide of the LSKs ([8-11]LSK) is inactive. Taken together with a comparison of the two LSK structures, the data suggest that the LSK active core resides between [8-11]LSK and [4-11]LSK. This is confirmed by considerable activity displayed by the sulfate analog of LSK-II, which contains an extra sulfate group on the Ser2 residue in the N-terminal region. Homology between the LSKs and molluscan cardioacceleratory and rectum contractile neuropeptide FMRF-amide and Met-enkephalin-Arg6-Phe7 is discussed. The insect LSKs may represent a molecular evolutionary link between the vertebrate gastrin/CCK family and this mammalian enkephalin.
 ...
PMID:Structural aspects of gastrin/CCK-like insect leucosulfakinins and FMRF-amide. 290 10

Human little gastrin-I is known to exhibit a high tendency to air-oxidation of its methionine-15 residue to the corresponding S-oxide derivative, with concomitant loss of biological activity. Since its leucine-15 analog, even if fully biologically active, differs significantly from the parent hormone in the immunological properties, the norleucine-15 and methoxinine-15 analogues were synthetized. For the required comparative analyses new syntheses of human little gastrin-I and of its leucine-15 analog were additionally elaborated. Upon an optimized condensation of the fragments, followed by the deprotection step, partition chromatography as well as preparative high-performance liquid chromatography led to the desired gastrins in satisfactory yields and high degree of purity as judged by the expected and known side products.
 ...
PMID:[Syntheses of human little gastrin-I and its leucine-15, norleucine-15 and methoxinine-15 analogs]. 684 Jul 3

The 15-methionine of human little gastrin I, prone to oxidation with concomitant loss of biological activity, has been replaced by leucine, norleucine and methoxinine, respectively. The resulting analogues exhibit acid secretory potencies practically undistinguishable from that of the parent hormone, whereas their immunoreactivity, as assayed with four different antisera raised against human little gastrin I, reflect to a significant extent the afforded modifications. Only [15-methoxinine]human little gastrin I retains practically the full reactivity for all antisera examined. The results suggest that this 15-methoxinine analogue is well suited for both biological and immunological studies.
 ...
PMID:Biological and immunological properties of human gastrin I analogues. 710 9

The syntheses of two analogues related to the C-terminal nonapeptide amide sequence 25-33 of cholecystokinin-pankreozymin are described. Based on the primary structure of the CCK-PZ-active caerulein and the experiences gained from the methionine replacement with leucine or norleucine in human little gastrin I, the analogues were designed by substituting methionine 28 with threonine, and methionine 31 with leucine and norleucine, respectively. Using a new method for the synthesis of tyrosine-O-sulfate-containing peptides, developed in our laboratory, and applying acid-labile side-chain protection in combination with the benzyloxycarbonyl group, the fully protected nonapeptide amide derivatives Z-Arg(Z2)-Asp(OBut)-Tyr-(SO3Ba1/2)-Thr(But)-Gly-Trp-Leu-Asp(OBut)-Phe-NH2 and Z-Arg(Z2)-Asp(OBut)-Tyr(SO3-Ba1/2)-Thr(But)-Gly-Trp-Nle-Asp(OBut)-Phe-NH2, were obtained. Upon hydrogenolytic and subsequent acidolytic removal of the protecting groups, followed by purification via chromatographic procedures the nonapeptide amides were isolated in satisfactory yields at a high degree of purity. In vivo and in vitro assays showed that a substitution of methionine 31 by norleucine with concomitant replacement of methionine 28 by threonine produced a fully active analogue, whereas for the threonine 28, leucine 31 analogue the pankreozymin-activity was lowered by a factor 10.
 ...
PMID:[Cholecystokinin-pancreozymin synthesis. Synthesis of [28-threonine,31-norleucine]- and [28-threonine,31-leucine]cholecystokinin-pancreozymin-(25-33)-nonapeptide]. 727 14


1 2 Next >>