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)

The mechanism by which partly digested protein (peptone) stimulates gastrin secretion was examined in isolated antral tissues with intact intramural innervation. In the isolated vascularly perfused rat stomach, luminal perfusion with 0.5% peptone increased gastrin (62 +/- 14 pg/min; P less than 0.01) and decreased somatostatin (74 +/- 19; P less than 0.01) secretion. The axonal blocker tetrodotoxin (TTX) abolished the gastrin and somatostatin responses indicating that the responses were neurally mediated. Atropine partly inhibited the gastrin response (50%) and converted the somatostatin response to an increase above basal level. The selective bombesin/gastrin-releasing peptide (GRP) antagonist [Leu13-psi(CH2NH)-Leu14]-bombesin partly inhibited the gastrin response (65%) and caused a further decrease in somatostatin secretion. A combination of atropine and the bombesin/GRP antagonist, like TTX, abolished the gastrin and somatostatin responses. The pattern of response to peptone in superfused antral segments was identical to that in the vascularly perfused stomach. In fundic segments that do not secrete gastrin, the somatostatin response to peptone alone and with various antagonists was identical to that in antral segments. The results indicate that peptone stimulates gastrin secretion by activating stimulatory cholinergic and bombesin/GRP neurons. Cholinergic neurons stimulate gastrin directly as well as indirectly by eliminating the inhibitory paracrine influence of somatostatin.
 ...
PMID:Peptone stimulates gastrin secretion from the stomach by activating bombesin/GRP and cholinergic neurons. 134 6

The present studies were directed to examine the effect of gastrin-releasing peptide (GRP) on beta-adrenergic stimulated gastrin release by cultured rat antral mucosa and to assess the anatomical relationship between gastrin cells and GRP nerves in rat and human antrum. Peptide-containing cells were identified by application of an avidin-biotin-peroxidase immunocytochemical double staining method utilizing antibodies to GRP and gastrin prepared in rabbits. Rat antral mucosa was cultured for 60 min and gastrin released into the culture medium was measured by radioimmunoassay. Inclusion of antibodies to GRP in culture medium did not affect carbachol-stimulated gastrin release, whereas isoproterenol-stimulated gastrin release into the medium was inhibited significantly by addition of GRP antiserum to the culture medium. GRP-containing neurons and axonal fibers were stained immunocytochemically with diaminobenzidine (reddish-brown specific staining) and were located in the lamina propria adjacent to and surrounding the main lobules of antral glands. After double staining utilizing 4-Cl-1-Naphthol as substrate, blue stained gastrin-containing cells were identified in the middle and deeper regions of antral glands in close proximity to GRP neuronal elements. These studies suggest that beta-adrenergic, but not cholinergic, stimulation of gastrin release is mediated, at least in part, through GRP. They also demonstrate intimate anatomical, as well as functional, relationships between gastrin cells and GRP-containing neurons.
 ...
PMID:Functional and anatomical relationships between antral gastrin cells and gastrin-releasing peptide neurons. 241 97

In order to understand better the neuronal circuitry involved in the regulation of gut functions, we have studied the distribution and projections of those enteric neurons in the rat intestines that contain vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), galanin, substance P (SP), calcitonin gene-related peptide (CGRP), gastrin releasing peptide (GRP), somatostatin and enkephalin. The origin of the peptide-containing nerve fibers was examined by immunocytochemistry after extrinsic denervation. Most of them were found to be intramural in origin, each population displaying its own characteristic topographic distribution. The projections of each neuronal population were studied immunocytochemically by examining the subsequent axonal degeneration after local severing of nervous pathways. This study revealed that myenteric neurons issue predominantly descending projections to other myenteric ganglia and to the muscle layers. Submucous neurons project to other submucous ganglia and to the mucosa and submucosa. Most of these neurons issue both ascending and descending projections. The projection distances varied considerably between the different neuronal populations, the majority being in the range of 4-10 mm. Myenteric GRP and galanin neurons in the small intestine issued the longest projections, 20 and 15 mm, respectively. The shortest projections were those issued from myenteric VIP/NPY neurons and submucosal galanin and GRP neurons in the small intestine and from submucosal VIP neurons in the large intestine (2 mm in length). On the whole our results on the projections of enteric neurons in the rat agree with observations in the guinea pig and dog. However, there are species differences that remain to be explained.
 ...
PMID:Projections of enteric peptide-containing neurons in the rat. 247 1

Somatostatin is found in both endocrine cells and nerve fibres of the gastrointestinal tract and has several inhibitory effects on the digestive tract. Somatostatin is a potent inhibitor of gastrin release; its secretion is regulated predominantly by the cholinergic pathway, which inhibits somatostatin and thus stimulates gastrin release. Gastric acid secretion is inhibited by both the paracrine and circulating peptide (hormonal) effects of somatostatin. Somatostatin secretion is a direct effect of acid on the somatostatin cell, since it is unaffected by the axonal blocker tetrodotoxin. Somatostatin antiserum eliminates the inhibitory effect of somatostatin and thus augments acid secretion. It therefore appears that somatostatin plays a physiological role in regulating gastric acid secretion, and it is possible that a lack of the inhibitory function of somatostatin is an aetiological factor in peptic ulcer disease. Postprandially, a rise in serum somatostatin concentration occurs which is twice as high with protein and fat as it is with carbohydrates. Several studies have shown that somatostatin inhibits nutrient absorption, indicating that somatostatin might be a physiological regulator in the homeostasis of ingested nutrients by modulating the intestinal absorption rate. Experiments have also demonstrated that somatostatin infusion inhibits intestinal motility; the interval between migrating myoelectric complexes is increased, and transit time is increased.
 ...
PMID:Physiological role of somatostatin in the digestive tract: gastric acid secretion, intestinal absorption, and motility. 287 6

The regulation of gastrin and somatostatin secretion by intraluminal chemicals was examined in an isolated vascularly perfused rat stomach, a preparation that maintains the integrity of intramural neural pathways and the polarity of stimulation. Intraluminal perfusion with alkaline solutions (0.1 M NaHCO3) increased gastrin secretion, whereas perfusion with acid solutions (pH 3.5-3.0) inhibited gastrin secretion. Perfusion with 0.5% or 5% peptone solutions stimulated gastrin secretion and inhibited somatostatin secretion. Both these responses were abolished by addition of the axonal blocker, tetrodotoxin (10(-6) M), to the vascular perfusate, from which it was concluded that gastrin and somatostatin responses induced by peptone were mediated by intramural neurons. These neurons were both cholinergic and noncholinergic, because addition of an optimal dose of atropine (10(-7) M) to the vascular perfusate inhibited only partially the gastrin response and converted the somatostatin response from decrease below basal levels--a typical cholinergic effect--to significant increase above basal levels. As shown previously, atropine had an identical effect on gastrin and somatostatin responses to transmural electrical stimulation of the antral region. The results are in accord with a model for the regulation of gastrin secretion by intramural cholinergic and noncholinergic neurons. A direct effect of intraluminal chemicals on gastrin and somatostatin cells was not detected in this study, but is not precluded.
 ...
PMID:Stimulation of gastrin secretion in vitro by intraluminal chemicals: regulation by intramural cholinergic and noncholinergic neurons. 614 51

The axonal transport velocity of immunoreactive cholecystokinin (CCK) was examined in the vagal and sciatic nerves of anesthetized cats after determination of the molecular form of CCK by sequence-specific radioimmunoassay and gel chromatography. Extracts of the peripheral nerve branches, corresponding spinal ganglia, brainstem and spinal cord, contained mainly CCK-8-like immunoreactivity. In addition a large molecular form eluted immediately after the void volume of Sephadex G-50 columns, and occasionally minor C-terminal fragments were discovered. A single vagal nerve and one medulla oblongata also contained gastrin-17-like material. Significant differences in the relative amounts of the molecular forms of CCK in the different regions and nerves were not apparent. The distally directed (anterograde) flux of CCK was found to be 78 fmol/h in the sciatic nerve and 50 fmol/h in the vagus. Significant retrograde transport was not detectable. Based on these figures the true velocity for the anterograde transport was estimated to be 7 mm/h for CCK in the vagus and 8 mm/h in the sciatic nerves. The results indicate that CCK-8-like peptides are rapidly transported distally without significant axonal processing of CCK precursors.
 ...
PMID:Cholecystokinin in feline vagal and sciatic nerves: concentration, molecular form and transport velocity. 619 57

Histamine accumulated in the ligated vagus nerve of the rat, both above and below the ligature; maximum accumulation was after 4 h. The finding is suggestive of axonal flow. Further evidence for histamine in peripheral nerves was obtained in experiments showing that the guinea-pig gut wall could be labelled with [3H]histamine. The experiments were carried out with isolated strips of stomach wall and taenia coli. Electrical stimulation released [3H]histamine from these specimens. The release could be blocked by Ca2+-free medium or by tetrodotoxin. The release was unaffected by vagal denervation or chemical sympathectomy (6-hydroxydopamine) but prevented by reserpinization. Gastrin-17 and cholecystokinin-39 released radioactivity by a tetrodotoxin-sensitive mechanism. The possible existence of a gastrin/cholecystokinin-sensitive neuronal pool of histamine in the gut wall offers a new perspective on the postulated role of histamine as a physiological stimulant of gastric acid secretion and might explain why H2-receptor antagonists block gastrin-stimulated acid secretion.
 ...
PMID:Neuronal histamine in the gut wall releasable by gastrin and cholecystokinin. 632 74

The distribution of gastrin/CCK-like immunoreactive material has been studied in the retrocerebral complex of Calliphora. The material reacts with antisera specific for the common COOH terminus of gastrin and CCK but not with N-terminal antisera. The three thoracic ganglia and the fused abdominal ganglia each contain a specific number of symmetrically arranged immunoreactive cells both dorsally and ventrally in pairs on either side of the midline in a sagittal plane. The neuropil of these ganglia also contains a considerable amount of immunoreactive fibres and droplets. Reconstructed axonal pathways suggest that some of the nerve fibres have their origins within the brain and/or the suboesophageal ganglion. Immunoreactive material may also be seen apparently leaving the thoracic ganglion posteriorly via the abdominal nerves, and there is strong evidence of a neurohaemal organ within the dorsal sheath in the region of the metathoracic and abdominal ganglia. There appears to be a direct correlation between the content of peptidergic material of cells and fibres and the age and diet of the flies. The corpus cardiacum contains COOH-terminal specific gastrin/CCK-like material within the intrinsic cells and in the neuropil. It is present also in the cardiac-recurrent nerve entering the corpus cardiacum anteriorly and in the nerves leaving the gland dorsoposteriorly, the aortic or cardiac nerves. It is not observed, however, in the nerves leaving the corpus cardiacum ventroposteriorly, the so-called oesophageal, gastric or crop-duct nerves. The corpus allatum and the hypocerebral ganglion do not contain immunoreactive material of this type. Gastrin/CCK-like and secretin-like immunoreactive materials appear to co-exist in the cells of the corpus cardiacum and co-existence of gastrin/CCK-like and pancreatic polypeptide-like substances occurs within certain cells of the thoracic ganglion.
 ...
PMID:Immunocytochemical mapping of gastrin/CCK-like peptides in the neuroendocrine system of the blowfly Calliphora vomitoria (Diptera). 638 21

The fine structural alteration in the gastric nerve fibers containing gastrin-releasing peptide (GRP) was studied in relation to the dynamics of gastrin-producing cells (G-cells) after truncal vagotomy in a rat model. The circulating gastrin levels were markedly elevated from the 1st day after vagotomy and the number of G-cells with positive immunoreaction for G17 and G34(1-15) was significantly increased in the vagotomized group. On the 3rd day after vagotomy, the G-cells showed conspicuous ultrastructural changes characterized by hypertrophy of the Golgi complexes and increased numbers of secretory granules. The GRP-positive nerve fibers formed a fine network in the gastric wall and were densely distributed in the oxyntic mucosa close to the blood vessels and showing varicosities composed of either small clear or GRP-positive large vesicles containing an electron-dense core. In the oxyntic mucosa of the vagotomized rats, axonal swelling of the nerves occurred on the 3rd day, and a depletion of GRP immunoreactivity was evidenced by a markedly decreased number of large-cored vesicles on the 7th day, when the serum GRP levels were also found to be markedly elevated. These findings indicate that the alteration in gastric nerve fibers containing GRP after truncal vagotomy may be related to hypergastrinemia and antral G-cell hyperplasia in the rat gastric mucosa.
 ...
PMID:Alteration in gastric nerve fibers containing gastrin-releasing peptide in relation to the gastrin-producing cell population after truncal vagotomy in a rat model. 764 Apr 68